Bypass of a psoralen DNA interstrand cross-link by DNA polymerases ?, ?, and ? in vitro.

ABSTRACT: Repair of DNA interstrand cross-links in mammalian cells involves several biochemically distinctive processes, including the release of one of the cross-linked strands and translesion DNA synthesis (TLS). In this report, we investigated the in vitro TLS activity of a psoralen DNA interstrand cross-link by three DNA repair polymerases, DNA polymerases ?, ?, and ?. DNA polymerase ? is capable of bypassing a psoralen cross-link with a low efficiency. Cell extracts prepared from DNA polymerase ? knockout mouse embryonic fibroblasts showed a reduced bypass activity of the psoralen cross-link, and purified DNA polymerase ? restored the bypass activity. In addition, DNA polymerase ? misincorporated thymine across the psoralen cross-link and DNA polymerase ? extended these mispaired primer ends, suggesting that DNA polymerase ? may serve as an inserter and DNA polymerase ? may play a role as an extender in the repair of psoralen DNA interstrand cross-links. The results demonstrated here indicate that multiple DNA polymerases could participate in TLS steps in mammalian DNA interstrand cross-link repair.

SUBMITTER: Smith LA 

PROVIDER: S-EPMC3516411 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature