1RYS

REPLICATION OF A CIS-SYN THYMINE DIMER AT ATOMIC RESOLUTION

Replaces:  1PM8

Summary for 1RYS

• Entry DOI: 10.2210/pdb1rys/pdb
• Related: 1RYR 1S0M 1S0N 1S0O 1S10
• Descriptor: 5'-D(*GP*GP*GP*GP*AP*AP*GP*GP*AP*TP*TP*CP*A)-3', 5'-D(*TP*CP*TP*TP*TP*GP*AP*AP*TP*CP*CP*TP*TP*CP*CP*CP*CP*C)-3', DNA polymerase IV, ... (8 entities in total)
• Functional Keywords: cpd dimer, lesion bypass, polymerase, transferase-dna complex, transferase/dna
• Biological source: Sulfolobus solfataricus
• Cellular location: Cytoplasm : Q97W02
• Total number of polymer chains: 6
• Total formula weight: 100683.84

Authors

Ling, H.,Boudsocq, F.,Plosky, B.,Woodgate, R.,Yang, W. (deposition date: 2003-12-22, release date: 2004-02-10, Last modification date: 2024-02-14)

Primary citation

Ling, H.,Boudsocq, F.,Plosky, B.,Woodgate, R.,Yang, W.
Replication of a Cis-Syn Thymine Dimer at Atomic Resolution
Nature, 424:1083-1087, 2003

PubMed Abstract: 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.

PubMed: 12904819
DOI: 10.1038/nature01919

Experimental method

X-RAY DIFFRACTION (2.03 Å)