3m9o is a 3 chain structure with sequence from Atcc 35091. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
[DPO4_SULSO] Poorly processive, error-prone DNA polymerase involved in untargeted mutagenesis. Copies undamaged DNA at stalled replication forks, which arise in vivo from mismatched or misaligned primer ends. These misaligned primers can be extended by PolIV. Exhibits no 3'-5' exonuclease (proofreading) activity. It is involved in translesional synthesis.[HAMAP-Rule:MF_01113]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Y-family DNA polymerases bypass Pt-GG, the cisplatin-DNA double-base lesion, contributing to the cisplatin resistance in tumour cells. To reveal the mechanism, we determined three structures of the Y-family DNA polymerase, Dpo4, in complex with Pt-GG DNA. The crystallographic snapshots show three stages of lesion bypass: the nucleotide insertions opposite the 3'G (first insertion) and 5'G (second insertion) of Pt-GG, and the primer extension beyond the lesion site. We observed a dynamic process, in which the lesion was converted from an open and angular conformation at the first insertion to a depressed and nearly parallel conformation at the subsequent reaction stages to fit into the active site of Dpo4. The DNA translocation-coupled conformational change may account for additional inhibition on the second insertion reaction. The structures illustrate that Pt-GG disturbs the replicating base pair in the active site, which reduces the catalytic efficiency and fidelity. The in vivo relevance of Dpo4-mediated Pt-GG bypass was addressed by a dpo-4 knockout strain of Sulfolobus solfataricus, which exhibits enhanced sensitivity to cisplatin and proteomic alterations consistent with genomic stress.
Structural insight into dynamic bypass of the major cisplatin-DNA adduct by Y-family polymerase Dpo4.,Wong JH, Brown JA, Suo Z, Blum P, Nohmi T, Ling H EMBO J. 2010 Jun 16;29(12):2059-69. Epub 2010 May 28. PMID:20512114[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
↑Wong JH, Brown JA, Suo Z, Blum P, Nohmi T, Ling H. Structural insight into dynamic bypass of the major cisplatin-DNA adduct by Y-family polymerase Dpo4. EMBO J. 2010 Jun 16;29(12):2059-69. Epub 2010 May 28. PMID:20512114 doi:10.1038/emboj.2010.101
