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REPLICATION OF A CIS-SYN THYMINE DIMER AT ATOMIC RESOLUTIONREPLICATION OF A CIS-SYN THYMINE DIMER AT ATOMIC RESOLUTION
Structural highlights
Evolutionary ConservationCheck, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedUltraviolet 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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