1ryr

From Proteopedia

Revision as of 23:51, 20 November 2007

REPLICATION OF A CIS-SYN THYMINE DIMER AT ATOMIC RESOLUTION

Overview

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.

About this Structure

1RYR is a Single protein structure of sequence from Sulfolobus solfataricus with CA and ATP as ligands. This structure superseeds the now removed PDB entry 1PM0. Active as DNA-directed DNA polymerase, with EC number 2.7.7.7 Full crystallographic information is available from OCA.

Reference

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

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