Structural basis of human DNA polymerase η-mediated chemoresistance to cisplatin.

ABSTRACT: Cisplatin (cis-diamminedichloroplatinum) and related compounds cause DNA damage and are widely used as anticancer agents. Chemoresistance to cisplatin treatment is due in part to translesion synthesis by human DNA polymerase η (hPol η). Here, we report crystal structures of hPol η complexed with intrastrand cisplatin-1,2-cross-linked DNA, representing four consecutive steps in translesion synthesis. In contrast to the generally enlarged and nondiscriminating active site of Y-family polymerases like Dpo4, Pol η is specialized for efficient bypass of UV-cross-linked pyrimidine dimers. Human Pol η differs from the yeast homolog in its binding of DNA template. To incorporate deoxycytidine opposite cisplatin-cross-linked guanines, hPol η undergoes a specific backbone rearrangement to accommodat

SUBMITTER: Zhao Y 

PROVIDER: S-EPMC3358888 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature