3MFI: DNA Polymerase Eta in Complex With a cis-syn Thymidine Dimer

Citation:
Abstract
DNA polymerase eta (Poleta) is unique among eukaryotic polymerases in its proficient ability for error-free replication through ultraviolet-induced cyclobutane pyrimidine dimers, and inactivation of Poleta (also known as POLH) in humans causes the variant form of xeroderma pigmentosum (XPV). We present the crystal structures of Saccharomyces cerevisiae Poleta (also known as RAD30) in ternary complex with a cis-syn thymine-thymine (T-T) dimer and with undamaged DNA. The structures reveal that the ability of Poleta to replicate efficiently through the ultraviolet-induced lesion derives from a simple and yet elegant mechanism, wherein the two Ts of the T-T dimer are accommodated in an active site cleft that is much more open than in other polymerases. We also show by structural, biochemical and genetic analysis that the two Ts are maintained in a stable configuration in the active site via interactions with Gln 55, Arg 73 and Met 74. Together, these features define the basis for Poleta's action on ultraviolet-damaged DNA that is crucial in suppressing the mutagenic and carcinogenic consequences of sun exposure, thereby reducing the incidence of skin cancers in humans.
PDB ID: 3MFIDownload
MMDB ID: 82952
PDB Deposition Date: 2010/4/2
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 1.76  Å
Source Organism:
Saccharomyces cerevisiae
Similar Structures:
Biological Unit for 3MFI: trimeric; determined by author and by software (PISA)
Molecular Components in 3MFI
Label Count Molecule
Protein (1 molecule)
1
DNA Polymerase ETA(Gene symbol: RAD30)
Molecule annotation
Nucleotides(2 molecules)
1
5'-d(*gp*tp*cp*cp*tp*cp*cp*cp*cp*tp*(doc))-3'
Molecule annotation
1
5'-d(*tp*ap*ap*(ttd)p*gp*ap*gp*gp*gp*gp*ap*gp*gp*ap*c)-3'
Molecule annotation
Chemicals (5 molecules)
1
1
2
2
3
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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