|1rys, resolution 2.03Å ()|
|Ligands:||, , ,|
|Gene:||DPO4 (Sulfolobus solfataricus)|
|Related:||1ryr, 1s0m, 1s0n, 1s0o, 1s10|
REPLICATION OF A CIS-SYN THYMINE DIMER AT ATOMIC RESOLUTION
Ultraviolet light damages DNA by catalysing covalent bond formation between adjacent pyrimidines, generating cis-syn cyclobutane pyrimidine dimers (CPDs) as the most common lesion. CPDs block DNA replication by high-fidelity DNA polymerases, but they can be efficiently bypassed by the Y-family DNA polymerase pol eta. Mutations in POLH encoding pol eta are implicated in nearly 20% of xeroderma pigmentosum, a human disease characterized by extreme sensitivity to sunlight and predisposition to skin cancer. Here we have determined two crystal structures of Dpo4, an archaeal pol eta homologue, complexed with CPD-containing DNA, where the 3' and 5' thymine of the CPD separately serves as a templating base. The 3' thymine of the CPD forms a Watson-Crick base pair with the incoming dideoxyATP, but the 5' thymine forms a Hoogsteen base pair with the dideoxyATP in syn conformation. Dpo4 retains a similar tertiary structure, but each unusual DNA structure is individually fitted into the active site for catalysis. A model of the pol eta-CPD complex built from the crystal structures of Saccharomyces cerevisiae apo-pol eta and the Dpo4-CPD complex suggests unique features that allow pol eta to efficiently bypass CPDs.
Replication of a cis-syn thymine dimer at atomic resolution., Ling H, Boudsocq F, Plosky BS, Woodgate R, Yang W, Nature. 2003 Aug 28;424(6952):1083-7. Epub 2003 Aug 6. PMID:12904819
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
1rys is a 6 chain structure with sequence from Sulfolobus solfataricus. This structure supersedes the now removed PDB entry 1pm8. The July 2007 RCSB PDB Molecule of the Month feature on Thymine Dimers by David S. Goodsell is 10.2210/rcsb_pdb/mom_2007_7. Full crystallographic information is available from OCA.