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1rys
From Proteopedia
| |||||||
| , resolution 2.03Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , and | ||||||
| Gene: | DPO4 (Sulfolobus solfataricus) | ||||||
| Activity: | DNA-directed DNA polymerase, with EC number 2.7.7.7 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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
1RYS is a Single protein structure of sequence from Sulfolobus solfataricus. This structure supersedes the now removed PDB entry 1PM8. The following page contains interesting information on the relation of 1RYS with [Thymine Dimers]. 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
Page seeded by OCA on Thu Mar 20 13:58:05 2008
Categories: DNA-directed DNA polymerase | Single protein | Sulfolobus solfataricus | Thymine Dimers | Boudsocq, F. | Ling, H. | Plosky, B. | Woodgate, R. | Yang, W. | ATP | CA | EDO | NA | Cpd dimer | Lesion bypass | Polymerase
