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Putative Roles of kin17, a Mammalian Protein Binding Curved DNA, in Transcription

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In bacteria, RecA protein is indispensable for recombination, mutagenesis and for the induction of SOS genes. Curiously, anti-RecA antibodies recognize kin17, a human nuclear Zn-finger protein of 45 kDa that preferentially binds to curved DNA and participates in a general response to diverse genotoxics. KIN17 gene is conserved from yeast to man and codes for a protein involved in DNA replication. Recent observations suggest that kin17 protein may also participate in RNA metabolism. Taken together all these data indicate the participation of kin17 protein in a pathway that harmonizes transcription, replication and repair in order to circumvent the topological constraints caused by unusually complex lesions like multiply damaged sites.


DNA conformation undergoes important and dynamic changes during transcription and replication. The molecular characterization of these changes is essential in predicting the progress of the cell cycle and when evaluating the consequences of the damage to mammalian cells caused by endogenous or environmental genotoxic agents. Therefore it is useful to identify proteins that recognize the particular structures formed during the metabolic processing of DNA. Several transcription factors and other nuclear proteins have been identified and shown to specifically recognize DNA deformations like cyclobutane pyrimidine dimers, platinum-DNA cross-links, cruciform DNA and curved regions.1-6 We have characterized a human protein that preferentially binds to curved DNA and is involved in DNA and RNA metabolism.

Identification of kin17 Protein

The analysis of human inherited disorders like xeroderma pigmentosum (xp) allowed the identification of genes coding for proteins that specifically bind to pyrimidine dimers and other types of DNA lesions.7-10 Some of these proteins belong to the machinery of DNA transcription or replication. These data provide a first image of the drastic effects that the modification of these proteins may have for the whole organism. In parallel, other human genes of DNA metabolism have been identified thanks to the genetic analysis of bacteria. In Escherichia coli bacteria, RecA protein is essential for homologous recombination, mutagenesis and the induction of the SOS response.11,12 The strong conservation of RecA protein among prokaryotes13,14 stimulated the search for analogous proteins in mammalian cells. Numerous eukaryotic proteins that are structural and/or functional homologues of RecA protein have been identified.15-25 All of them seem to evolve from a common ancestral protein but only a small subset of these RecA-like proteins may form helical filaments on DNA. Indeed, the functional divergence of RecA-like proteins is enormous, the members of this family being involved in different DNA transactions.26 Anti-RecA antibodies cross-react with nuclear proteins from plant or mammalian cells.27-33 Interestingly, the cross-reacting material is localized in structures directly involved in DNA transactions during mitosis or meiosis (e.g., the synaptonemal complex, the stroma or meiotic nodules).29,30,33 In mammalian cells and tissues, the cross-reacting material is nuclear and their levels are low in quiescent cells as compared to proliferating cells. Genotoxic agents like mitomycin C (MMC) induced a striking increase of these antigens inside the nucleus. 27 Considering the cross-reactivity with anti-RecA antibodies we proposed the generic name of kin proteins (from immunological kinship to RecA protein). The screening of expression libraries using antibodies raised against the E. coli RecA protein allowed us the isolation of recA genes from Streptococcus pneumoniae,34 Streptomyces ambofaciens35 and Gram+ bacteria.36 Therefore, we used this approach to isolate 17 cDNA fragments from a mouse embryo cDNA library. The clone number 17 gave the strongest cross-reactivity and was used to isolate the full-length cDNA. The encoded protein has a primary structure different to that of RecA and is different from all the proteins reported in databases. The lack of information on the biological role of this gene led us to call it KIN17 gene.37,38

Molecular Characterization of kin17 Protein

Modular Nature of kin17 Protein

The mouse kin17 protein, has a calculated molecular weight of 44,726 and an isolelectric point of 9.3. The primary structure contains the following domains that are located in hydrophilic helix regions of the protein.37,39 (Fig. 1A):

Figure 1A. Conservation of the modular structure of kin17 protein.

Figure 1A

Conservation of the modular structure of kin17 protein. Multiple sequence alignment of five metazoan kin17 proteins. The Zinc finger motif that mediates the interaction with DNA is enclosed with a box and named motif I. The RecA homologous region corresponding (more...)

  1. a Zn-finger domain of 23 residues of the type x2Cx12Hx5H between residues 28 and 50 which mediated DNA recognition.38,39
  2. an active bipartite nuclear localization signal of 31 residues (236 and 266)38 that accounts for the nuclear localization of kin17 protein in mammalian tissues.40-44
  3. a KOW motif (residues 330 to 363) supposed to participate in transcription elongation.45,46

Orthologs of KIN17 gene have been reported from yeast to humans, however the family of encoded proteins do not present striking homologies with other proteins.42 The evolutionary conservation of kin17 protein structure is significant since there are several mammalian nuclear proteins involved in important DNA processes, like tumour suppressor p5347 and DNA-damage sensor protein poly(ADP-ribose) polymerase48 which lack a yeast counterpart, indicating that some important DNA transactions are particular to mammals. A central fragment of 39 residues which is highly conserved between the human and mouse kin17 proteins (residues 163 to 201, Fig. 1A) has a sequence similarity with the fragment 308-346, within the Cterminal domain of RecA protein (residues 270-352),32 as shown in Figure 1B. The core of RecA protein (residues 31-269) is followed by a smaller C-terminal domain that appears as a lobe on the surface of the RecA filament.49 This lobe shifts after binding of nucleotides.50-54 A major antigenic determinant is located between residues 260 and 330 of RecA protein.55 Although the last 24 residues of the C-terminus are disordered in the proposed crystal structure of RecA, genetic and biochemical data indicate a role in modulating DNA binding, probably in regulating the access of double stranded (ds) DNA to the presynaptic filament.56,57 Accordingly, the deletion of a C-terminal fragment of RecA protein reduces the efficiency of recombination, 58 probably because it nucleates to double-stranded DNA much more frequently than does the wild-type protein57 resulting in increased sensitivity to MMC in vivo.59-61 In vitro this deletion enhanced binding to duplex DNA.56,61

Figure 1B. Conservation of the modular structure of kin17 protein.

Figure 1B

Conservation of the modular structure of kin17 protein. Structure of the antigenic determinant common to kin17 and RecA proteins. The region of human and mouse kin17 proteins from the amino acid L163 to E201 is shown and compared with the C-terminal fragment (more...)

Molecular Bases of the Cross-Reactivity

The cross-reactivity between kin17 protein and anti-RecA antibodies is due to a major antigenic determinant located in the core of kin17 protein between amino acids 129 and 228. The deletion of this fragment avoids the cross-reactivity and dramatically affects the intranuclear localization. Indeed, the truncated kin17 protein forms large nucleoplasmic clusters that strongly interact with nuclear components.62 This data indicates that the strong antigenic determinant is part of a functional domain.

Interaction between kin17 Protein and Curved DNA

The finger motif of kin17 protein binds Zn. The resultant Zn-finger mediates the interaction with double- and single-stranded (ss) DNA. More importantly, kin17 protein binds preferentially to pBR322 fragments carrying curved segments with an efficiency that seems to be correlated with the magnitude of DNA curvature.39 Milot et al showed that chromosomal illegitimate recombination junctions in mammals are associated with the presence of curved DNA,63 Curved DNA contains runs of adenines distributed regularly at one run per helical repeat and has a reduced electrophoretic mobility. The functional importance of curve DNA in several biological relevant processes will be discussed in the other chapters of this book. In the case of kin17 protein produced in bacteria, the relevance of the interaction with curved DNA was further assessed in vitro by using fragments found at illegitimate recombination. Indeed, Stary and Sarasin isolated several hot spots of illegitimate recombination from an HeLa derived- cell line carrying a single copy of an SV40 shuttle vector. In these cells, the overexpression of SV40 T-antigen produce heterogenous circular DNA molecules carrying the integrated vector and the boundary cellular DNA associated with palindromes, A + T-rich DNA segments, alternating purine/pyrimidine sequences and Alu family repeats.64 Other sites of integration of polyomavirus in the mouse genome were tested in parallel. They confirmed a preferential binding of kin17 protein to curved DNA leading to the suggestion that this protein may be involved in the illegitimate recombination process.65,66 The binding to curve DNA is mediated by a domain located in the core of kin17 protein between residues 71 and 281.39 In vitro, the base composition of DNA may modify its interaction with the kin17 protein (Tran et al, 2004, submitted). The binding of kin17 protein to DNA has been also observed in cultured human cells.67 As described below, the binding of kin17 protein to curved DNA was further confirmed in vivo by overexpressing the mouse kin17 protein in E. coli.65,66

Evidence for the Participation of kin17 Protein in Transcription

Expression of kin17 Protein in E. coli and Trans Species Complementation

Devoret and colleagues showed that kin17 protein produced in bacteria under the control of a Tac promoter is able to regulate gene expression by binding to curved DNA regions.66 They used H-NS-deficient strains of E. coli. H-NS protein is a major component of the nucleoid which binds to curved DNA and regulates the expression of at least 36 genes. Among these H-NS upregulates the flhDC gene, encoding flagellin, the major structural component of flagellae responsible for cell motility. The expression of kin17 protein in H-NS-deficient bacteria increases the synthesis of flagellin and leads to the recovery of motility. The same H-NS protein downregulates in vivo the bgl operon as kin17 protein does. However, not all H-NS functions can be recovered by the expression of kin17 protein. This is not surprising because even in two closely related species like E. coli and Salmonella only partial complementation of H-NS are observed. Whatever the complementation may be, these data indicate that kin17 protein may be involved in the regulation of gene expression in mammalian cells.66 In mouse or human cells, the up- or downregulation of kin17 protein induced important changes in the pattern of gene expression leading to a complex pleiotrophic phenotype suggesting a role in transcription. 67- 70 Furthermore, in vivo, kin17 protein is detected in all the cell types that compose the male mouse germinal tissue (Fig. 2). It is distributed in intranuclear clusters and interacts directly with RNA and DNA. In agreement with this data, Rappsilver et al have identified kin17 protein as part of the human spliceosome by large-scale proteomic analysis.71 Indeed, under native conditions, a fraction of kin17 protein was co-purified with the fraction containing polyA+ RNAs pointing to a direct role in RNA processing.72

Figure 2. In vivo detection of kin17 protein in adult mouse testis sections.

Figure 2

In vivo detection of kin17 protein in adult mouse testis sections. Kin17 protein was detected using the monoclonal antibody 58 (mAb k58) and revealed with 3,3'-diaminobenzidine tetrahydrochloride (DAB) brown staining as reported., The sections were counterstained (more...)

Preferential Expression during Proliferation

In cultured cells, KIN17 gene expression reaches its highest level during cell proliferation and falls in confluent cells in a way similar to that of the group of late-growth related genes. In proliferating cells, kin17 protein is located in nuclear foci.68 This particular intranuclear distribution indicates its participation in a nuclear network required during cell growth.40,41,73 However, the physiologic level of kin17 protein is tightly regulated since its ectopic overexpression triggers a strong deformation of nuclear morphology and is lethal for mammalian cells.68,69 The overexpression of deletion mutants indicates that the C-terminal end of kin17 protein may interact with the nuclear matrix and is essential for the formation of the large intranuclear clusters. Indeed, a fraction of the endogenous nuclear kin17 protein is strongly anchored in the nuclear matrix.74 Interestingly, one of the partners of kin17 protein in the nuclear networks is the viral T-antigen (T-Ag).75 In certain cell types T-Ag is also associated with the nuclear matrix in the heterogeneous nuclear riboucleoprotein (hnRNP) network including peri- and interchromatin fibrils which are the centres of pre-mRNA splicing.76

Physical Interaction with SV40 T Antigen

The physical contact with kin17 protein takes place through the T2 region (amino acids 168 to 383) located in the NH2-terminal region of T antigen.75 The binding of T-Ag to the viral origin of replication enhances this interaction. The residues involved lie in the major DNA-binding domain of T-Ag which interacts with p53 and DNA polymerase α. The kin17 protein inhibits T-Ag-dependent DNA replication and suggests that these two proteins form part of a nuclear complex in vivo.75 This tallies with the fact that nuclear kin17 protein molecules are in equilibrium between a fraction dispersed through the nucleoplasm and fractions bound to chromatin, DNA or nuclear matrix.74 The molecules of kin17 protein move from the nucleoplasmic dispersed form to the bound form during cell proliferation.77

UVC Irradiation of Non-Replicating Cells Triggers the Intranuclear Accumulation of kin17 Protein

UVC-irradiation of arrested mouse or primary human fibroblasts boosts KIN17 gene expression to its maximal values within around 16 hours.42,78 In human cells, 50 to 75% of DNA lesions caused by UVC are eliminated within 2 hours by nucleotide excision repair (NER) in the so-called “early phase”;79 the remaining lesions are processed during a “late phase” by other mechanisms.80,81 Since KIN17 gene expression begins to increase 7 hours after irradiation, we conclude that this gene may be involved in transactions that helps to circumvent lesions not resolved by NER in the late phase of the response, as defined by Herrlich et al.82 Since in these cells DNA synthesis is arrested, it remains to be determined whether kin17 protein acts directly on the lesions or if it indirectly activates the expression of repair proteins.

Identifying the Mechanism of the UVC-Induced Upregulation

The fact that UVC and ionizing radiation (IR) upregulate KIN17 gene by two distinct pathways that are independent of the ataxia telengiectasia mutated gene (ATM) prompted us to identify other regulating factors. Two transcription factors, AP-1 and NFκβ, control several other UVC-responsive genes via the protein kinase C (PKC) pathway.83 However, phorbol ester treatment does not affect KIN17 RNA expression in BALB/c 3T3 or in mouse lymphoma cells.78 Similarly, p53 protein controls the expression of nearly 100 genes implicated in the UVC response. Some of them display expression kinetics similar to those of KIN17 gene84-86 but normal and p53-deficient cells display a similar UV-induced upregulation of KIN17 gene.87,88 Finally, Weiss et al showed that the mouse Hus1 gene, a component of the cellular machinery that responds to stalled DNA replication and DNA damage, is not involved in the UV-induced upregulation of KIN17 RNA.89

The Integrity of Two DNA Repair Genes Is Required for the Upregulation of KIN17 Gene Expression after UVC Irradiation

We determined the expression of the human KIN17 gene in primary fibroblasts from xeroderma pigmentosum patients, an autosomal recessive cancer-prone inherited disorder provoked by the inactivation of one of the seven XP genes (XPA to XPG). XP patients (NER-deficient) are extremely sensitive to sunlight compared to NER-proficient individuals. NER possesses two major overlapping subpathways: global genome repair (GGR) and transcription coupled repair (TCR). The earliest step of GGR is lesion recognition by a complex formed by two proteins: xeroderma pigmentosum group C (XPC) and one of the human homologues to Rad23 (HHR23B),90 followed by the recruitment of the transcription factor II H (TFIIH) and XPG, XPA, replication protein A (RPA), excision repair complementation class-1 (ERCC-1) and XPF. Human primary fibroblasts from XPA and XPC patients are unable to trigger KIN17 gene expression after UVC-irradiation although they present a similar upregulation of p53 protein, of P21 and GADD45 RNA. This observation was further confirmed using XP44RO, a cell line established from a testicular melanoma of an XPC patient that also failed to upregulate KIN17 gene after irradiation. The introduction of a retroviral vector carrying the normal XPC cDNA in XP44RO cells fully restored their capacity to repair DNA and to trigger KIN17 gene expression after irradiation. This indicates a direct relation between the repair capacity of the cell and the upregulation of this gene. Primary fibroblasts from an XPA patient are also unable to induce KIN17 gene expression. These data indicate that the activities of XPA and XPC proteins are required to trigger KIN17 gene expression after UV. This response is strictly dependent on GGR, indicating that the primary signal that leads to the upregulation of KIN17 gene and other UVC-responsive genes is a subset of the complexes formed at the site of DNA lesions during GGR.88 Strikingly, this is the first case of a UVC-inducible response which is strictly dependent on GGR. The fact that human XPC protein translocates very rapidly (within 5 minutes) to the sites containing UV lesions and that lesion binding seems to trigger an overall intranuclear stabilization of XPC protein further supports this hypothesis.91

The Knock Down of Human KIN17 Gene Increases Radiosensitivity of Human Cells

RKO cells present a great number of kin17 protein molecules/cell as compared with normal human fibroblasts or other tumour-derived cells. Considering this fact, we introduced an episomal vector carrying a human KIN17 cDNA in an antisense orientation. Three stable clones presented 70-80% reduction in the level of kin17 protein were called RASK (from RKO antisense KIN17) and were further characterized.67 These clones have a plating efficiency 15-fold lower than those observed for the control clones, and display a reduced proliferation rate, indicating that decreased levels of kin17 protein strongly affect cell growth. RASK cells accumulate in early and mid-S phase. Only a few cells were detected in late S phase, suggesting that low kin17 protein levels result in a better entry into S phase with some difficulties in progressing through the S phase. However, irradiation of RKO and RASK cells at 6 Gy does not affect the γ-rayinduced G2 arrest, indicating that kin17 protein is not essential at this checkpoint.67 As expected, RASK cells are 4- to 5-fold more radiosensitive than the parental RKO cells,70 indicating that low levels of kin17 protein lead to important changes in the expression profile of genes relevant for cell survival.

Speculative Remarks

The interaction RecA-DNA is modulated by the C-terminal domain of the protein.61 This domain plays its regulatory role by interacting with other domains of the RecA filament coated on DNA. Although RecA protein does not preferentially recognize curved DNA, it does bind, like kin17, to ds, ssDNA and ssRNA.92-94 In kin17 protein, the domain homologous to the Cterminal domain of RecA participates in the preferential recognition of curved DNA. This property acquired during evolution may be helpful to detect a particular DNA (or most probably RNA) structure. During evolution, kin17 protein also acquired a KOW domain suggesting a role in transcription elongation. We hypothesize that under physiological conditions kin17 protein may be involved in elongation or splicing by recognizing particular structures on RNA. This interaction may provoke conformational changes that will increase the stability of the complex and will facilitate the recruitment of other nuclear proteins. Interestingly enough, RecA protein is able to assimilate RNA into duplex DNA leading to the formation of an Rloop.94 Kasahara et al proposed that R-loops serve as origins of bi-directional chromosome replication.94

Evidence Pointing to a Role of kin17 Protein in DNA Replication

Molecular Analysis of Deletion Mutants

The deletion of the core DNA-binding domain of kin17 protein leads to the formation of large intranuclear clusters with a shape different from those formed by the wild-type protein and produces important deleterious effects.62,68 The deletion of this region abolishes the binding to curved DNA whereas deletion of the Zn-finger domain or of the C-terminal end does not affect this interaction.39,62 The ectopic expression of kin17 protein inhibits T-Ag-dependent DNA replication, indicating a strong interference with T-antigen or with the nuclear areas on which the synthesis of viral DNA takes place.68 As mentioned, RKO cells presenting decreased amounts of kin17 protein display a disruption in the S phase progression, together with a significant decrease in clonogenic growth.67 This results suggest the involvement of kin17 protein in DNA replication.

Biochemical Detection of kin17 Protein in DNA Replication Complexes

We analyzed the properties of kin17 protein in its native state in human cells. Gel filtration of total protein extracts showed that the human kin17 protein is present in three complexes with molecular masses corresponding to Mr 400,000 (I), 600,000 (II) and 1,800,000 (III). RPA protein coelutes in complexes II and III. Treatment of human cells with HU arrests them at the G1-S border and increases the molecular weight of the kin17-containing complexes together with a relocalization of kin17 protein in large intranuclear clusters (Fig. 3). L-mimosine (MIMO) and HU trigger a similar effect in RKO cells.77 The other drugs affecting DNA replication and producing a redistribution of kin17 protein are the following: aphidicolin (APH) which inhibits DNA polymerase α and δ; camptothecin (CPT) which interferes with the sealing activity of DNA topoisomerase I producing double strand breaks (DSBs), and etoposide (VP16), a specific inhibitor of DNA topoisomerase II. 24 hours after treatment with any of these drugs the nuclear concentration of kin17 protein increased and formed intranuclear clusters which are easily detectable by immunocytochemical detection (Fig. 3A). As expected, the drug treatment strongly modified the cell cycle as shown by the comparison of DNA synthesis in the population of mock treated and treated cells (Fig. 3B). In treated cells, the intranuclear concentration of anchored kin17 protein increased as compared with that of mock treated cells as shown by western detection of nuclear proteins like kin17, RPA 70, PCNA and p34cdc2 (Fig. 3C).

Figure 3C. Detection of proteins HSAkin17, RPA70, PCNA and p34cdc2 in the nuclear fraction of treated cells.

Figure 3C

Detection of proteins HSAkin17, RPA70, PCNA and p34cdc2 in the nuclear fraction of treated cells. HCT116 cells at 50% confluence were treated with etoposide, camptothecine, aphidicolin, hydroxyurea, 1-mimosine or nocodazol at the indicated doses. 24 h (more...)

Figure 3A. Cell cycle arrest triggers the accumulation of human kin17 protein in large intranuclear clusters as shown by immunocytochemical detection of this protein and DNA.

Figure 3A

Cell cycle arrest triggers the accumulation of human kin17 protein in large intranuclear clusters as shown by immunocytochemical detection of this protein and DNA. HCT116 cells were seeded for four days and thereafter treated with different drugs known (more...)

Figure 3B. Monitoring the cell cycle arrest by flow cytometry of BrdU-labelled cells.

Figure 3B

Monitoring the cell cycle arrest by flow cytometry of BrdU-labelled cells. 24 h after treatment with nocodazol, aphidicolin, hydroxyurea, l-mimosine, camptothecine or etoposide, HCT116 cells were pulse-labelled with 30 mM bromodeoxyuridine (BrdU) for (more...)

Intranuclear Modification of Protein Complexes during the Cell Cycle

Treatment of proliferating HeLa cells with L-mimosine for 24h followed by drug removal resulted in a synchronized population which rapidly re-entered into the S phase. A time dependent increase in kin17, cyclin B and p34cdc2 levels were observed until completion of the S phase. This should be correlated with the re-initiation of DNA replication.74 In parallel kin17 protein is detected in DNA replication foci attached to the nuclear matrix of HeLa cells. The removal of more than 80% of total DNA did not affect the association with other nuclear proteins. The in vivo protein-protein cross-linking confirmed the association with the nuclear matrix during all the phases of the cell cycle, indicating that the “nucleoplasmic pool” of kin17 protein could serve as a “stock” that may later be associated with both chromatin and/or nuclear matrix during DNA replication.74 It is possible that the nuclear accumulation of kin17 protein leads to an increase in the chromatin-bound fraction in order to facilitate the DNA replication process in spite of the presence of multiply damaged sites or other DNA lesions.74 Further work will be required to precise the role of kin17 protein in replication. Although in mammals several aspects of this process remains yet to be elucidated, research on viruses indicates that replication initiation proteins belongs to the class of RNA-binding proteins involved in splicing.95 This observation opens the possibility to use kin17 protein as a tool to precisely describe the molecular steps of replication initiation in human cells during the response to genotoxic agents.


We have identified a nuclear protein that participates in the response to severe lesions created by genotoxics on chromatin. Since this protein recognizes curved DNA and other particular RNA structures and forms high molecular weight complexes, we assume that it may be important for the formation of clusters around the unrepaired remaining lesions. We suggest that this process is a “last chance pathway” that gives the opportunity to restart DNA replication before activation of cell death. The recognition of topological constraints created by several types of DNA damage may perturb the accurate replication of DNA therefore decreasing fidelity and helping to generate biological diversity (see Fig. 4).96

Figure 4. Participation of human kin17 protein in a general response to genotoxic agents.

Figure 4

Participation of human kin17 protein in a general response to genotoxic agents. The involvement of kin17 protein in different responses to genotoxic agents has already been reported.,,,,,,, After genotoxic injury, UV or IR, there are two possibilities (more...)


The authors are indebted to B. Dutrillaux, C. Créminon, Y. Frobert, J. Grassi, F. Harper, E. Pichard and E. Puvion for advice and support, and to M. Plaisance, P. Lamourette and M.C. Nevers for their efficient help in producing monoclonal antibodies. Work in the authors' laboratory was supported by the Commissariat à l'énergie atomique (CEA) and Electricité de France Contract 8702.


Toney JH, Donahue BA, Kellett PJ. et al. Isolation of cDNAs encoding a human protein that binds selectively to DNA modified by the anticancer drug cis-diamminedichloroplatinum(II) Proc Natl Acad Sci USA. 1989;86:8328–8332. [PMC free article: PMC298274] [PubMed: 2530581]
Donahue BA, Augot M, Bellon SF. et al. Characterization of a DNA damage-recognition protein from mammalian cells that binds specifically to intrastrand d(GpG) and d(ApG) DNA adducts of the anticancer drug cisplatin. Biochemistry. 1990;29:5872–5880. [PubMed: 2383564]
Donahue BA, Yin S, Taylor JS. et al. Transcript cleavage by RNA polymerase II arrested by a cyclobutane pyrimidine dimer in the DNA template. Proc Natl Acad Sci USA. 1994;91:8502–8506. [PMC free article: PMC44634] [PubMed: 8078911]
Coates PJ, Save V, Ansari B. et al. Demonstration of DNA damage/repair in individual cells using in situ end labelling: association of p53 with sites of DNA damage. J Pathol. 1995;176:19–26. [PubMed: 7542331]
Bianchi ME, Beltrame M, Paonessa G. Specific recognition of cruciform DNA by nuclear protein HMG1. Science. 1989;243:1056–1059. [PubMed: 2922595]
Pierro P, Capaccio L, Gadaleta G. The 25 kDa protein recognizing the rat curved region upstream of the origin of the L-strand replication is the rat homologue of the human mitochondrial transcription factor A. FEBS Lett. 1999;457:307–310. [PubMed: 10471798]
Setlow RB, Setlow JK. Evidence that ultraviolet-induced thymine dimers in DNA cause biological damage. Proc Natl Acad Sci USA. 1962;48:1250–1257. [PMC free article: PMC220940] [PubMed: 13910967]
Cleaver JE. Defective repair replication of DNA in xeroderma pigmentosum. Nature. 1968;218:652–656. [PubMed: 5655953]
Tanaka K, Miura N, Satokata I. et al. Analysis of a human DNA excision repair gene involved in group A xeroderma pigmentosum and containing a zinc-finger domain. Nature. 1990;348:73–76. [PubMed: 2234061]
Friedberg EC, Walker GC, Siede W. Human hereditary diseases with defective processing of DNA damage. In: DNA Repair and Mutagenesis. Washington DC: ASM Press. 1995:633–685.
Eggleston AK, West SC. Exchanging partners: recombination in E. coli. Trends Genet. 1996;12:20–26. [PubMed: 8741856]
Sommer S, Bailone A, Devoret R. The appearance of the UmuD'C protein complex in Escherichia coli switches repair from homologous recombination to SOS mutagenesis. Mol Microbiol. 1993;10:963–971. [PubMed: 7934872]
Cox MM. Recombinational DNA repair in bacteria and the RecA protein. Prog Nucleic Acid Res Mol Biol. 1999;63:311–366. [PubMed: 10506835]
Eisen JA. The RecA protein as a model molecule for molecular systematic studies of bacteria: Comparison of trees of RecAs and 16S rRNAs from the same species. J Mol Evol. 1995;41:1105–1123. [PMC free article: PMC3188426] [PubMed: 8587109]
Sato S, Kobayashi T, Hotta Y. et al. Characterization of a mouse recA-like gene specifically expressed in testis. DNA Res. 1995;2:147–150. [PubMed: 8581742]
Sato S, Hotta Y, Tabata S. Structural analysis of a recA-like gene in the genome of Arabidopsis thaliana. DNA Res. 1995;2:89–93. [PubMed: 7584052]
Yoshida K, Kondoh G, Matsuda Y. et al. The mouse RecA-like gene Dmc1 is required for homologous chromosome synapsis during meiosis. Mol Cell. 1998;1:707–718. [PubMed: 9660954]
Takahashi E, Matsuda Y, Hori T. et al. Chromosome mapping of the human (RECA) and mouse (Reca) homologs of the yeast RAD51 and Escherichia coli recA genes to human (15q15.1) and mouse (2F1) chromosomes by direct R-banding fluorescence in situ hybridization. Genomics. 1994;19:376–378. [PubMed: 8188269]
Brendel V, Brocchieri L, Sandler SJ. et al. Evolutionary comparisons of RecA-like proteins across all major kingdoms of living organisms. J Mol Evol. 1997;44:528–541. [PubMed: 9115177]
McKee BD, Ren X, Hong C. A recA-like gene in Drosophila melanogaster that is expressed at high levels in female but not male meiotic tissues. Chromosoma. 1996;104:479–488. [PubMed: 8625736]
Pittman DL, Weinberg LR, Schimenti JC. Identification, characterization, and genetic mapping of Rad51d, a new mouse and human RAD51/RecA-related gene. Genomics. 1998;49:103–111. [PubMed: 9570954]
Terasawa M, Shinohara A, Hotta Y. et al. Localization of RecA-like recombination proteins on chromosomes of the lily at various meiotic stages. Genes Dev. 1995;9:925–934. [PubMed: 7774810]
Yoshimura Y, Morita T, Yamamoto A. et al. Cloning and sequence of the human RecA-like gene cDNA. Nucleic Acids Res. 1993;21:1665. [PMC free article: PMC309378] [PubMed: 8479919]
Morita T, Yoshimura Y, Yamamoto A. et al. A mouse homolog of the Escherichia coli recA and Saccharomyces cerevisiae RAD51 genes. Proc Natl Acad Sci USA. 1993;90:6577–6580. [PMC free article: PMC46975] [PubMed: 8341671]
Aihara H, Ito Y, Kurumizaka H. et al. An interaction between a specified surface of the C-terminal domain of RecA protein and double-stranded DNA for homologous pairing. J Mol Biol. 1997;274:213–221. [PubMed: 9398528]
Yang S, VanLoock MS, Yu X. et al. Comparison of bacteriophage T4 UvsX and human Rad51 filaments suggests that RecA-like polymers may have evolved independently. J Mol Biol. 2001;312:999–1009. [PubMed: 11580245]
Angulo JF, Moreau PL, Maunoury R. et al. KIN, a mammalian nuclear protein immunologically related to E. coli RecA protein. Mutat Res. 1989;217:123–134. [PubMed: 2493134]
Higashitani A, Tabata S, Ogawa T. et al. ATP-independent strand transfer protein from murine spermatocytes, spermatids, and spermatozoa. Exp Cell Res. 1990;186:317–323. [PubMed: 2404773]
Bashkirov VI, Loseva EF, Savchenko GV. et al. Antibodies against Escherichia coli RecA protein reveal two nuclear proteins in bovine spermatocytes which interact with synaptonemal complex structures of meiotic chromosomes of various eukaryotic organisms. Genetika. 1993;29:1953–1968. [PubMed: 7509766]
Cerutti H, Osman M, Grandoni P. et al. A homolog of Escherichia coli RecA protein in plastids of higher plants. Proc Natl Acad Sci USA. 1992;89:8068–8072. [PMC free article: PMC49857] [PubMed: 1518831]
Cerutti H, Ibrahim HZ, Jagendorf AT. Treatment of pea (Pisum sativum L.) protoplasts with DNA-damaging agents induces a 39-kilodalton chloroplast protein immunologically related to Escherichia coli RecA. Plant Physiol. 1993;102:155–163. [PMC free article: PMC158758] [PubMed: 8108495]
Tissier A, Kannouche P, Biard DS. et al. The mouse Kin-17 gene codes for a new protein involved in DNA transactions and is akin to the bacterial RecA protein. Biochimie. 1995;77:854–860. [PubMed: 8824764]
Anderson LK, Offenberg HH, Verkuijlen WM. et al. RecA-like proteins are components of early meiotic nodules in lily. Proc Natl Acad Sci USA. 1997;94:6868–6873. [PMC free article: PMC21251] [PubMed: 11038554]
Martin B, Ruellan JM, Angulo JF. et al. Identification of the recA gene of Streptococcus pneumoniae. Nucleic Acids Res. 1992;20:6412. [PMC free article: PMC334537] [PubMed: 1475203]
Aigle B, Holl AC, Angulo JF. et al. Characterization of two Streptomyces ambofaciens recA mutants: identification of the RecA protein by immunoblotting. FEMS Microbiol Lett. 1997;149:181– 187. [PubMed: 9141659]
Borchiellini P, Angulo J, Bertolotti R. Genes encoding mammalian recombinases: Cloning approach with anti-RecA antibodies. Biogenic Amines. 1997;13:195–215.
Angulo JF, Rouer E, Benarous R. et al. Identification of a mouse cDNA fragment whose expressed polypeptide reacts with anti-recA antibodies. Biochimie. 1991;73:251–256. [PubMed: 1715759]
Angulo JF, Rouer E, Mazin A. et al. Identification and expression of the cDNA of KIN17, a zincfinger gene located on mouse chromosome 2, encoding a new DNA-binding protein. Nucleic Acids Res. 1991;19:5117–5123. [PMC free article: PMC328864] [PubMed: 1923796]
Mazin A, Timchenko T, Menissier-de-Murcia J. et al. Kin17, a mouse nuclear zinc finger protein that binds preferentially to curved DNA. Nucleic Acids Res. 1994;22:4335–4341. [PMC free article: PMC331959] [PubMed: 7937163]
Araneda S, Angulo J, Devoret R. et al. Identification of a Kin nuclear protein immunologically related to RecA protein in the rat CNS. C R Acad Sci III. 1993;316:593–597. [PubMed: 8019879]
Araneda S, Angulo J, Touret M. et al. Preferential expression of kin, a nuclear protein binding to curved DNA, in the neurons of the adult rat. Brain Res. 1997;762:103–113. [PubMed: 9262164]
Kannouche P, Mauffrey P, Pinon-Lataillade G. et al. Molecular cloning and characterization of the human KIN17 cDNA encoding a component of the UVC response that is conserved among metazoans. Carcinogenesis. 2000;21:1701–1710. [PubMed: 10964102]
Biard DSF, Saintigny Y, Maratrat M. et al. Enhanced expression of the kin17 protein immediately after low doses of ionizing radiation. Radiat Res. 1997;147:442–450. [PubMed: 9092924]
Biard DSF, Saintigny Y, Maratrat M. et al. Differential expression of the Hskin17 protein during differentiation of in vitro reconstructed human skin. Arch Dermatol Res. 1997;289:448–456. [PubMed: 9266022]
Kyrpides NC, Woese CR, Ouzounis CA. KOW: a novel motif linking a bacterial transcription factor with ribosomal proteins. Trends Biochem Sci. 1996;21:425–426. [PubMed: 8987397]
Ponting CP. Novel domains and orthologues of eukaryotic transcription elongation factors. Nucleic Acids Res. 2002;30:3643–3652. [PMC free article: PMC137420] [PubMed: 12202748]
Kazianis S, Gan L, Della Coletta L. et al. Cloning and comparative sequence analysis of TP53 in Xiphophorus fish hybrid melanoma models. Gene. 1998;212:31–38. [PubMed: 9661661]
de Murcia G, Menissier de Murcia J. Poly(ADP-ribose) polymerase: a molecular nick-sensor. Trends Biochem Sci. 1994;19:172–176. [PubMed: 8016868]
Yu X, Egelman EH. Removal of the RecA C-terminus results in a conformational change in the RecA-DNA filament. J Struct Biol. 1991;106:243–254. [PubMed: 1804279]
Eggler AL, Lusetti SL, Cox MM. The C terminus of the Escherichia coli RecA protein modulates the DNA binding competition with single-stranded DNA-binding protein. J Biol Chem. 2003;278:16389–16396. [PubMed: 12598538]
Story RM, Steitz TA. Structure of the recA protein-ADP complex. Nature. 1992;355:374–376. [PubMed: 1731253]
Story RM, Weber IT, Steitz TA. The structure of the E. coli recA protein monomer and polymer. Nature. 1992;355:318–325. [PubMed: 1731246]
VanLoock MS, Yu X, Yang S. et al. ATP-mediated conformational changes in the RecA filament. Structure (Camb) 2003;11:187–196. [PubMed: 12575938]
Yu X, Jacobs SA, West SC. et al. Domain structure and dynamics in the helical filaments formed by RecA and Rad51 on DNA. Proc Natl Acad Sci USA. 2001;98:8419–8424. [PMC free article: PMC37452] [PubMed: 11459984]
Krivi GG, Bittner ML, Rowold Jr E. et al. Purification of recA-based fusion proteins by immunoadsorbent chromatography. Characterization of a major antigenic determinant of Escherichia coli recA protein. J Biol Chem. 1985;260:10263–10267. [PubMed: 2410422]
Benedict RC, Kowalczykowski SC. Increase of the DNA strand assimilation activity of recA protein by removal of the C terminus and structure-function studies of the resulting protein fragment. J Biol Chem. 1988;263:15513–15520. [PubMed: 2971666]
Tateishi S, Horii T, Ogawa T. et al. C-terminal truncated Escherichia coli RecA protein RecA5327 has enhanced binding affinities to single- and double-stranded DNAs. J Mol Biol. 1992;223:115–129. [PubMed: 1731064]
Larminat F, Defais M. Modulation of the SOS response by truncated RecA proteins. Mol Gen Genet. 1989;216:106–112. [PubMed: 2525224]
Sedgwick SG, Yarranton GT. Cloned truncated recA genes in E. coli. I. Effect on radiosensitivity and recA+ dependent processes. Mol Gen Genet. 1982;185:93–98. [PubMed: 7045578]
Yarranton GT, Sedgwick SG. Cloned truncated recA genes in E. coli II.Effects of truncated gene. Mol Gen Genet. 1982;185:99–104. [PubMed: 6283314]
Lusetti SL, Wood EA, Fleming CD. et al. C-terminal Deletions of the Escherichia coli RecA Protein. Characterisation of in vivo and in vitro effects. J Biol Chem. 2003;278:16372–16380. [PubMed: 12598539]
Kannouche P, Pinon-Lataillade G, Mauffrey P. et al. Overexpression of kin17 protein forms intranuclear foci in mammalian cells. Biochimie. 1997;79:599–606. [PubMed: 9466698]
Milot E, Belmaaza A, Wallenburg JC. et al. Chromosomal illegitimate recombination in mammalian cells is associated with intrinsically bent DNA elements. EMBO J. 1992;11:5063–5070. [PMC free article: PMC556984] [PubMed: 1464328]
Stary A, Sarasin A. Molecular analysis of DNA junctions produced by illegitimate recombination in human cells. Nucleic Acids Res. 1992;20:4269–4274. [PMC free article: PMC334135] [PubMed: 1324477]
Mazin A, Milot E, Devoret R. et al. KIN17, a mouse nuclear protein, binds to bent DNA fragments that are found at illegitimate recombination junctions in mammalian cells. Mol Gen Genet. 1994;244:435–438. [PubMed: 8078469]
Timchenko T, Bailone A, Devoret R. Btcd, a mouse protein that binds to curved DNA, can substitute in Escherichia coli for H-NS, a bacterial nucleoid protein. EMBO J. 1996;15:3986–3992. [PMC free article: PMC452118] [PubMed: 8670903]
Biard DS, Miccoli L, Despras E. et al. Ionizing radiation triggers chromatin-bound kin17 complex formation in human cells. J Biol Chem. 2002;277:19156–19165. [PubMed: 11880372]
Kannouche P, Angulo JF. Overexpression of kin17 protein disrupts nuclear morphology and inhibits the growth of mammalian cells. J Cell Sci. 1999;112:3215–3224. [PubMed: 10504327]
Biard DS, Kannouche P, Lannuzel-Drogou C. et al. Ectopic expression of (Mm)Kin17 protein inhibits cell proliferation of human tumor-derived cells. Exp Cell Res. 1999;250:499–509. [PubMed: 10413603]
Despras E, Miccoli L, Creminon C. et al. Depletion of KIN17, a human DNA replication protein, increases the radiosensitivity of RKO cells. Radiat Res. 2003;159:748–758. [PubMed: 12751957]
Rappsilber J, Ryder U, Lamond AI. et al. Large-scale proteomic analysis of the human spliceosome. Genome Res. 2002;12:1231–1245. [PMC free article: PMC186633] [PubMed: 12176931]
Pinon-Lataillade G, Masson C, Bernardino-Sgherri J. et al. KIN17 encodes an RNA-binding protein and is expressed during mouse spermatogenesis. J Cell Sci. 2004;117:3691–3702. [PubMed: 15252136]
Araneda S, Mermet N, Verjat T. et al. Expression of Kin17 and 8-OxoG DNA glycosylase in cells of rodent and quail central nervous system. Brain Res Bull. 2001;56:139–146. [PubMed: 11704351]
Miccoli L, Biard DS, Frouin I. et al. Selective interactions of human kin17 and RPA proteins with chromatin and the nuclear matrix in a DNA damage- and cell cycle-regulated manner. Nucleic Acids Res. 2003;31:4162–4175. [PMC free article: PMC165974] [PubMed: 12853634]
Miccoli L, Biard DSF, Creminon C. et al. Human kin17 protein directly interacts with the SV40 large T antigen and inhibits DNA replication. Cancer Res. 2002;62:5425–5436. [PubMed: 12359749]
Puvion E, Duthu A, Harper F. et al. Intranuclear distribution of SV40 large T-antigen and transformation-related protein p53 in abortively infected cells. Exp Cell Res. 1988;177:73–89. [PubMed: 2839350]
Biard DS, Miccoli L, Despras E. et al. Participation of kin17 protein in replication factories and in other DNA transactions mediated by high molecular weight nuclear complexes. Mol Cancer Res. 2003;1:519–531. [PubMed: 12754299]
Kannouche P, Pinon-Lataillade G, Tissier A. et al. The nuclear concentration of kin17, a mouse protein that binds to curved DNA, increases during cell proliferation and after UV irradiation. Carcinogenesis. 1998;19:781–789. [PubMed: 9635863]
Jensen KA, Smerdon MJ. DNA repair within nucleosome cores of UV-irradiated human cells. Biochemistry. 1990;29:4773–4782. [PubMed: 2364058]
Dresler SL, Gowans BJ, Robinson-Hill RM. et al. Involvement of DNA polymerase δ in DNA repair synthesis in human fibroblasts at late times after ultraviolet irradiation. Biochemistry. 1988;27:6379–6383. [PubMed: 3146346]
Tornaletti S, Pfeifer GP. UV damage and repair mechanisms in mammalian cells. Bioessays. 1996;18:221–228. [PubMed: 8867736]
Herrlich P, Blattner C, Knebel A. et al. Nuclear and non-nuclear targets of genotoxic agents in the induction of gene expression. Shared principles in yeast, rodents, man and plants. Biol Chem. 1997;378:1217–1229. [PubMed: 9426181]
Nishizuka Y. Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. Science. 1992;258:607–614. [PubMed: 1411571]
Maltzman W, Czyzyk L. UV irradiation stimulates levels of p53 cellular tumor antigen in nontransformed mouse cells. Mol Cell Biol. 1984;4:1689–1694. [PMC free article: PMC368974] [PubMed: 6092932]
Smith ML, Fornace Jr AJ. p53-mediated protective responses to UV irradiation. Proc Natl Acad Sci USA. 1997;94:12255–12257. [PMC free article: PMC33783] [PubMed: 9356435]
May P, May E. Twenty years of p53 research: structural and functional aspects of the p53 protein. Oncogene. 1999;18:7621–7636. [PubMed: 10618702]
Blattner C, Kannouche P, Litfin M. et al. UV-induced stabilization of c-fos and other short-lived mRNAs. Mol Cell Biol. 2000;20:3616–3625. [PMC free article: PMC85654] [PubMed: 10779351]
Masson C, Menaa F, Pinon-Lataillade G. et al. Global genome repair is required to activate KIN17, a UVC-responsive gene involved in DNA replication. Proc Natl Acad Sci USA. 2003;100:616–621. [PMC free article: PMC141045] [PubMed: 12525703]
Weiss RS, Enoch T, Leder P. Inactivation of mouse Hus1 results in genomic instability and impaired responses to genotoxic stress. Genes Dev. 2000;14:1886–1898. [PMC free article: PMC316817] [PubMed: 10921903]
Sugasawa K, Ng JM, Masutani C. et al. Xeroderma pigmentosum group C protein complex is the initiator of global genome nucleotide excision repair. Mol Cell. 1998;2:223–232. [PubMed: 9734359]
Ng JM, Vermeulen W, Van Der Horst GT. et al. A novel regulation mechanism of DNA repair by damage-induced and RAD23-dependent stabilization of xeroderma pigmentosum group C protein. Genes Dev. 2003;17:1630–1645. [PMC free article: PMC196135] [PubMed: 12815074]
Kirkpatrick DP, Rao BJ, Radding CM. RNA-DNA hybridization promoted by E. coli RecA protein. Nucleic Acids Res. 1992;20:4339–4346. [PMC free article: PMC334145] [PubMed: 1380698]
Zaitsev EN, Kowalczykowski SC. A novel pairing process promoted by Escherichia coli RecA protein: inverse DNA and RNA strand exchange. Genes Dev. 2000;14:740–749. [PMC free article: PMC316457] [PubMed: 10733533]
Kasahara M, Clikeman JA, Bates DB. et al. RecA protein-dependent R-loop formation in vitro. Genes Dev. 2000;14:360–365. [PMC free article: PMC316363] [PubMed: 10673507]
Stenlund A. Initiation of DNA replication: Lessons from viral initiator proteins. Nat Rev Mol Cell Biol. 2003;4:777–785. [PubMed: 14504622]
Aravind L, Walker DR, Koonin EV. Conserved domains in DNA repair proteins and evolution of repair systems. Nucleic Acids Res. 1999;27:1223–1242. [PMC free article: PMC148307] [PubMed: 9973609]
Masson C, Menaa F, Pinon-Lataillade G. et al. Identification of KIN (KIN17), a human gene encoding a nuclear DNA-binding protein, as a novel component of the TP53-independent response to ionizing radiation. Radiat Res. 2001;156:535–544. [PubMed: 11604067]
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