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Recurrently Breaking Genes in Neural Progenitors: Potential Roles of DNA Breaks in Neuronal Function, Degeneration and Cancer.

Alt FW, Wei PC, Schwer B.

In: Jaenisch R, Zhang F, Gage F, editors. Genome Editing in Neurosciences [Internet]. Cham (CH): Springer; 2017.
2017 Sep 15.


Pillars Article: Restoration of T Cell Development in RAG-2-Deficient Mice by Functional TCR Transgenes. Science. 1993. 259: 822-825.

Shinkai Y, Koyasu S, Nakayama KI, Murphy KM, Loh DY, Reinherz EL, Alt FW.

J Immunol. 2019 Mar 1;202(5):1317-1320. No abstract available.


Defective DNA damage repair leads to frequent catastrophic genomic events in murine and human tumors.

Ratnaparkhe M, Wong JKL, Wei PC, Hlevnjak M, Kolb T, Simovic M, Haag D, Paul Y, Devens F, Northcott P, Jones DTW, Kool M, Jauch A, Pastorczak A, Mlynarski W, Korshunov A, Kumar R, Downing SM, Pfister SM, Zapatka M, McKinnon PJ, Alt FW, Lichter P, Ernst A.

Nat Commun. 2018 Nov 12;9(1):4760. doi: 10.1038/s41467-018-06925-4.


Neural blastocyst complementation enables mouse forebrain organogenesis.

Chang AN, Liang Z, Dai HQ, Chapdelaine-Williams AM, Andrews N, Bronson RT, Schwer B, Alt FW.

Nature. 2018 Nov;563(7729):126-130. doi: 10.1038/s41586-018-0586-0. Epub 2018 Oct 10.


RAG Chromatin Scanning During V(D)J Recombination and Chromatin Loop Extrusion are Related Processes.

Lin SG, Ba Z, Alt FW, Zhang Y.

Adv Immunol. 2018;139:93-135. doi: 10.1016/ Epub 2018 Aug 27.


Parp3 promotes long-range end joining in murine cells.

Layer JV, Cleary JP, Brown AJ, Stevenson KE, Morrow SN, Van Scoyk A, Blasco RB, Karaca E, Meng FL, Frock RL, Tivey T, Kim S, Fuchs H, Chiarle R, Alt FW, Roberts SA, Weinstock DM, Day TA.

Proc Natl Acad Sci U S A. 2018 Oct 2;115(40):10076-10081. doi: 10.1073/pnas.1801591115. Epub 2018 Sep 13.


DNA double-strand breaks as drivers of neural genomic change, function, and disease.

Alt FW, Schwer B.

DNA Repair (Amst). 2018 Nov;71:158-163. doi: 10.1016/j.dnarep.2018.08.019. Epub 2018 Aug 23. Review.


Guiding a mutator in antibody diversification.

Tian M, Alt FW.

Cell Res. 2018 Oct;28(10):963-964. doi: 10.1038/s41422-018-0085-8. No abstract available.


Glycan Masking Focuses Immune Responses to the HIV-1 CD4-Binding Site and Enhances Elicitation of VRC01-Class Precursor Antibodies.

Duan H, Chen X, Boyington JC, Cheng C, Zhang Y, Jafari AJ, Stephens T, Tsybovsky Y, Kalyuzhniy O, Zhao P, Menis S, Nason MC, Normandin E, Mukhamedova M, DeKosky BJ, Wells L, Schief WR, Tian M, Alt FW, Kwong PD, Mascola JR.

Immunity. 2018 Aug 21;49(2):301-311.e5. doi: 10.1016/j.immuni.2018.07.005. Epub 2018 Jul 31.


Kinase-dependent structural role of DNA-PKcs during immunoglobulin class switch recombination.

Crowe JL, Shao Z, Wang XS, Wei PC, Jiang W, Lee BJ, Estes VM, Alt FW, Zha S.

Proc Natl Acad Sci U S A. 2018 Aug 21;115(34):8615-8620. doi: 10.1073/pnas.1808490115. Epub 2018 Aug 2.


DNA melting initiates the RAG catalytic pathway.

Ru H, Mi W, Zhang P, Alt FW, Schatz DG, Liao M, Wu H.

Nat Struct Mol Biol. 2018 Aug;25(8):732-742. doi: 10.1038/s41594-018-0098-5. Epub 2018 Jul 30.


CTCF-Binding Elements Mediate Accessibility of RAG Substrates During Chromatin Scanning.

Jain S, Ba Z, Zhang Y, Dai HQ, Alt FW.

Cell. 2018 Jun 28;174(1):102-116.e14. doi: 10.1016/j.cell.2018.04.035. Epub 2018 May 24.


Three classes of recurrent DNA break clusters in brain progenitors identified by 3D proximity-based break joining assay.

Wei PC, Lee CS, Du Z, Schwer B, Zhang Y, Kao J, Zurita J, Alt FW.

Proc Natl Acad Sci U S A. 2018 Feb 20;115(8):1919-1924. doi: 10.1073/pnas.1719907115. Epub 2018 Feb 5.


DNA double-strand break response factors influence end-joining features of IgH class switch and general translocation junctions.

Panchakshari RA, Zhang X, Kumar V, Du Z, Wei PC, Kao J, Dong J, Alt FW.

Proc Natl Acad Sci U S A. 2018 Jan 23;115(4):762-767. doi: 10.1073/pnas.1719988115. Epub 2018 Jan 8.


Mechanism of tandem duplication formation in BRCA1-mutant cells.

Willis NA, Frock RL, Menghi F, Duffey EE, Panday A, Camacho V, Hasty EP, Liu ET, Alt FW, Scully R.

Nature. 2017 Nov 30;551(7682):590-595. doi: 10.1038/nature24477. Epub 2017 Nov 22.


Histone methyltransferase MMSET promotes AID-mediated DNA breaks at the donor switch region during class switch recombination.

Nguyen HV, Dong J, Panchakshari RA, Kumar V, Alt FW, Bories JC.

Proc Natl Acad Sci U S A. 2017 Dec 5;114(49):E10560-E10567. doi: 10.1073/pnas.1701366114. Epub 2017 Nov 20.


Ectopic expression of RAD52 and dn53BP1 improves homology-directed repair during CRISPR-Cas9 genome editing.

Paulsen BS, Mandal PK, Frock RL, Boyraz B, Yadav R, Upadhyayula S, Gutierrez-Martinez P, Ebina W, Fasth A, Kirchhausen T, Talkowski ME, Agarwal S, Alt FW, Rossi DJ.

Nat Biomed Eng. 2017 Nov;1(11):878-888. doi: 10.1038/s41551-017-0145-2. Epub 2017 Oct 9.


Synthetic lethality between murine DNA repair factors XLF and DNA-PKcs is rescued by inactivation of Ku70.

Xing M, Bjørås M, Daniel JA, Alt FW, Oksenych V.

DNA Repair (Amst). 2017 Sep;57:133-138. doi: 10.1016/j.dnarep.2017.07.008. Epub 2017 Jul 26.


AID Recognizes Structured DNA for Class Switch Recombination.

Qiao Q, Wang L, Meng FL, Hwang JK, Alt FW, Wu H.

Mol Cell. 2017 Aug 3;67(3):361-373.e4. doi: 10.1016/j.molcel.2017.06.034. Epub 2017 Jul 27.


Sequence intrinsic somatic mutation mechanisms contribute to affinity maturation of VRC01-class HIV-1 broadly neutralizing antibodies.

Hwang JK, Wang C, Du Z, Meyers RM, Kepler TB, Neuberg D, Kwong PD, Mascola JR, Joyce MG, Bonsignori M, Haynes BF, Yeap LS, Alt FW.

Proc Natl Acad Sci U S A. 2017 Aug 8;114(32):8614-8619. doi: 10.1073/pnas.1709203114. Epub 2017 Jul 26.


Characterization of physiological defects in adult SIRT6-/- mice.

Peshti V, Obolensky A, Nahum L, Kanfi Y, Rathaus M, Avraham M, Tinman S, Alt FW, Banin E, Cohen HY.

PLoS One. 2017 Apr 27;12(4):e0176371. doi: 10.1371/journal.pone.0176371. eCollection 2017.


Phosphatidylinositol 3-kinase δ blockade increases genomic instability in B cells.

Compagno M, Wang Q, Pighi C, Cheong TC, Meng FL, Poggio T, Yeap LS, Karaca E, Blasco RB, Langellotto F, Ambrogio C, Voena C, Wiestner A, Kasar SN, Brown JR, Sun J, Wu CJ, Gostissa M, Alt FW, Chiarle R.

Nature. 2017 Feb 23;542(7642):489-493. doi: 10.1038/nature21406. Epub 2017 Feb 15.


Human Ig knockin mice to study the development and regulation of HIV-1 broadly neutralizing antibodies.

Verkoczy L, Alt FW, Tian M.

Immunol Rev. 2017 Jan;275(1):89-107. doi: 10.1111/imr.12505. Review.


An Ectopic CTCF Binding Element Inhibits Tcrd Rearrangement by Limiting Contact between Vδ and Dδ Gene Segments.

Chen L, Zhao L, Alt FW, Krangel MS.

J Immunol. 2016 Oct 15;197(8):3188-3197. Epub 2016 Sep 9.


Induction of HIV Neutralizing Antibody Lineages in Mice with Diverse Precursor Repertoires.

Tian M, Cheng C, Chen X, Duan H, Cheng HL, Dao M, Sheng Z, Kimble M, Wang L, Lin S, Schmidt SD, Du Z, Joyce MG, Chen Y, DeKosky BJ, Chen Y, Normandin E, Cantor E, Chen RE, Doria-Rose NA, Zhang Y, Shi W, Kong WP, Choe M, Henry AR, Laboune F, Georgiev IS, Huang PY, Jain S, McGuire AT, Georgeson E, Menis S, Douek DC, Schief WR, Stamatatos L, Kwong PD, Shapiro L, Haynes BF, Mascola JR, Alt FW.

Cell. 2016 Sep 8;166(6):1471-1484.e18. doi: 10.1016/j.cell.2016.07.029.


PAXX and XLF DNA repair factors are functionally redundant in joining DNA breaks in a G1-arrested progenitor B-cell line.

Kumar V, Alt FW, Frock RL.

Proc Natl Acad Sci U S A. 2016 Sep 20;113(38):10619-24. doi: 10.1073/pnas.1611882113. Epub 2016 Sep 6.


Orientation-specific RAG activity in chromosomal loop domains contributes to Tcrd V(D)J recombination during T cell development.

Zhao L, Frock RL, Du Z, Hu J, Chen L, Krangel MS, Alt FW.

J Exp Med. 2016 Aug 22;213(9):1921-36. doi: 10.1084/jem.20160670. Epub 2016 Aug 15.


Highly sensitive and unbiased approach for elucidating antibody repertoires.

Lin SG, Ba Z, Du Z, Zhang Y, Hu J, Alt FW.

Proc Natl Acad Sci U S A. 2016 Jul 12;113(28):7846-51. doi: 10.1073/pnas.1608649113. Epub 2016 Jun 27.


Pillars Article: A Functional T3 Molecule Associated with a Novel Heterodimer on the Surface of Immature Human Thymocytes. Nature. 1986. 322: 179-181.

Bank I, DePinho RA, Brenner MB, Cassimeris J, Alt FW, Chess L.

J Immunol. 2016 May 1;196(9):3514-6. Epub 2016 Apr 18. No abstract available.


Detecting DNA double-stranded breaks in mammalian genomes by linear amplification-mediated high-throughput genome-wide translocation sequencing.

Hu J, Meyers RM, Dong J, Panchakshari RA, Alt FW, Frock RL.

Nat Protoc. 2016 May;11(5):853-71. doi: 10.1038/nprot.2016.043. Epub 2016 Mar 31.


Transcription-associated processes cause DNA double-strand breaks and translocations in neural stem/progenitor cells.

Schwer B, Wei PC, Chang AN, Kao J, Du Z, Meyers RM, Alt FW.

Proc Natl Acad Sci U S A. 2016 Feb 23;113(8):2258-63. doi: 10.1073/pnas.1525564113. Epub 2016 Feb 12.


Long Neural Genes Harbor Recurrent DNA Break Clusters in Neural Stem/Progenitor Cells.

Wei PC, Chang AN, Kao J, Du Z, Meyers RM, Alt FW, Schwer B.

Cell. 2016 Feb 11;164(4):644-55. doi: 10.1016/j.cell.2015.12.039.


Sequential activation and distinct functions for distal and proximal modules within the IgH 3' regulatory region.

Garot A, Marquet M, Saintamand A, Bender S, Le Noir S, Rouaud P, Carrion C, Oruc Z, Bébin AG, Moreau J, Lebrigand K, Denizot Y, Alt FW, Cogné M, Pinaud E.

Proc Natl Acad Sci U S A. 2016 Feb 9;113(6):1618-23. doi: 10.1073/pnas.1514090113. Epub 2016 Feb 1.


Chromosomal Loop Domains Direct the Recombination of Antigen Receptor Genes.

Hu J, Zhang Y, Zhao L, Frock RL, Du Z, Meyers RM, Meng FL, Schatz DG, Alt FW.

Cell. 2015 Nov 5;163(4):947-59. doi: 10.1016/j.cell.2015.10.016. Epub 2015 Oct 22.


Sequence-Intrinsic Mechanisms that Target AID Mutational Outcomes on Antibody Genes.

Yeap LS, Hwang JK, Du Z, Meyers RM, Meng FL, Jakubauskaitė A, Liu M, Mani V, Neuberg D, Kepler TB, Wang JH, Alt FW.

Cell. 2015 Nov 19;163(5):1124-1137. doi: 10.1016/j.cell.2015.10.042. Epub 2015 Nov 12.


Orientation-specific joining of AID-initiated DNA breaks promotes antibody class switching.

Dong J, Panchakshari RA, Zhang T, Zhang Y, Hu J, Volpi SA, Meyers RM, Ho YJ, Du Z, Robbiani DF, Meng F, Gostissa M, Nussenzweig MC, Manis JP, Alt FW.

Nature. 2015 Sep 3;525(7567):134-139. doi: 10.1038/nature14970. Epub 2015 Aug 26.


Related Mechanisms of Antibody Somatic Hypermutation and Class Switch Recombination.

Hwang JK, Alt FW, Yeap LS.

Microbiol Spectr. 2015 Feb;3(1):MDNA3-0037-2014. doi: 10.1128/microbiolspec.MDNA3-0037-2014. Review.


A Rapid Embryonic Stem Cell-Based Mouse Model for B-cell Lymphomas Driven by Epstein-Barr Virus Protein LMP1.

Ba Z, Meng FL, Gostissa M, Huang PY, Ke Q, Wang Z, Dao MN, Fujiwara Y, Rajewsky K, Zhang B, Alt FW.

Cancer Immunol Res. 2015 Jun;3(6):641-9. doi: 10.1158/2326-6066.CIR-15-0058. Epub 2015 May 1.


An oncogenic role for alternative NF-κB signaling in DLBCL revealed upon deregulated BCL6 expression.

Zhang B, Calado DP, Wang Z, Fröhler S, Köchert K, Qian Y, Koralov SB, Schmidt-Supprian M, Sasaki Y, Unitt C, Rodig S, Chen W, Dalla-Favera R, Alt FW, Pasqualucci L, Rajewsky K.

Cell Rep. 2015 May 5;11(5):715-26. doi: 10.1016/j.celrep.2015.03.059. Epub 2015 Apr 23.


Aberrant TCRδ rearrangement underlies the T-cell lymphocytopenia and t(12;14) translocation associated with ATM deficiency.

Jiang W, Lee BJ, Li C, Dubois RL, Gostissa M, Alt FW, Zha S.

Blood. 2015 Apr 23;125(17):2665-8. doi: 10.1182/blood-2015-01-622621. Epub 2015 Feb 26.


CTCF-binding elements 1 and 2 in the Igh intergenic control region cooperatively regulate V(D)J recombination.

Lin SG, Guo C, Su A, Zhang Y, Alt FW.

Proc Natl Acad Sci U S A. 2015 Feb 10;112(6):1815-20. doi: 10.1073/pnas.1424936112. Epub 2015 Jan 26.


Genome-wide detection of DNA double-stranded breaks induced by engineered nucleases.

Frock RL, Hu J, Meyers RM, Ho YJ, Kii E, Alt FW.

Nat Biotechnol. 2015 Feb;33(2):179-86. doi: 10.1038/nbt.3101. Epub 2014 Dec 15.


Convergent transcription at intragenic super-enhancers targets AID-initiated genomic instability.

Meng FL, Du Z, Federation A, Hu J, Wang Q, Kieffer-Kwon KR, Meyers RM, Amor C, Wasserman CR, Neuberg D, Casellas R, Nussenzweig MC, Bradner JE, Liu XS, Alt FW.

Cell. 2014 Dec 18;159(7):1538-48. doi: 10.1016/j.cell.2014.11.014. Epub 2014 Dec 4.


Developmental propagation of V(D)J recombination-associated DNA breaks and translocations in mature B cells via dicentric chromosomes.

Hu J, Tepsuporn S, Meyers RM, Gostissa M, Alt FW.

Proc Natl Acad Sci U S A. 2014 Jul 15;111(28):10269-74. doi: 10.1073/pnas.1410112111. Epub 2014 Jun 30.


Mechanisms that can promote peripheral B-cell lymphoma in ATM-deficient mice.

Tepsuporn S, Hu J, Gostissa M, Alt FW.

Cancer Immunol Res. 2014 Sep;2(9):857-66. doi: 10.1158/2326-6066.CIR-14-0090. Epub 2014 Jun 9.


Reprint of "Functional overlaps between XLF and the ATM-dependent DNA double strand break response".

Kumar V, Alt FW, Oksenych V.

DNA Repair (Amst). 2014 May;17:52-63. doi: 10.1016/j.dnarep.2014.04.004. Epub 2014 Apr 24.


Precise and in situ genetic humanization of 6 Mb of mouse immunoglobulin genes.

Macdonald LE, Karow M, Stevens S, Auerbach W, Poueymirou WT, Yasenchak J, Frendewey D, Valenzuela DM, Giallourakis CC, Alt FW, Yancopoulos GD, Murphy AJ.

Proc Natl Acad Sci U S A. 2014 Apr 8;111(14):5147-52. doi: 10.1073/pnas.1323896111. Epub 2014 Mar 25.


Functional overlaps between XLF and the ATM-dependent DNA double strand break response.

Kumar V, Alt FW, Oksenych V.

DNA Repair (Amst). 2014 Apr;16:11-22. doi: 10.1016/j.dnarep.2014.01.010. Epub 2014 Feb 20. Review.


IgH class switching exploits a general property of two DNA breaks to be joined in cis over long chromosomal distances.

Gostissa M, Schwer B, Chang A, Dong J, Meyers RM, Marecki GT, Choi VW, Chiarle R, Zarrin AA, Alt FW.

Proc Natl Acad Sci U S A. 2014 Feb 18;111(7):2644-9. doi: 10.1073/pnas.1324176111. Epub 2014 Feb 3.


A systematic analysis of recombination activity and genotype-phenotype correlation in human recombination-activating gene 1 deficiency.

Lee YN, Frugoni F, Dobbs K, Walter JE, Giliani S, Gennery AR, Al-Herz W, Haddad E, LeDeist F, Bleesing JH, Henderson LA, Pai SY, Nelson RP, El-Ghoneimy DH, El-Feky RA, Reda SM, Hossny E, Soler-Palacin P, Fuleihan RL, Patel NC, Massaad MJ, Geha RS, Puck JM, Palma P, Cancrini C, Chen K, Vihinen M, Alt FW, Notarangelo LD.

J Allergy Clin Immunol. 2014 Apr;133(4):1099-108. doi: 10.1016/j.jaci.2013.10.007. Epub 2013 Nov 28.

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