Bypass of a psoralen DNA interstrand cross-link by DNA polymerases β, l, and κ in Vitro

Leigh A. Smith, Alena V. Makarova, Laura Samson, Katherine E. Thiesen, Alok Dhar, Tadayoshi Bessho

Research output: Contribution to journalArticle

17 Scopus citations

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 β, κ, and l. DNA polymerase β is capable of bypassing a psoralen cross-link with a low efficiency. Cell extracts prepared from DNA polymerase β knockout mouse embryonic fibroblasts showed a reduced bypass activity of the psoralen cross-link, and purified DNA polymerase β restored the bypass activity. In addition, DNA polymerase l misincorporated thymine across the psoralen cross-link and DNA polymerase κ extended these mispaired primer ends, suggesting that DNA polymerase l may serve as an inserter and DNA polymerase κ 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.

Original languageEnglish (US)
Pages (from-to)8931-8938
Number of pages8
JournalBiochemistry
Volume51
Issue number44
DOIs
StatePublished - Nov 6 2012

ASJC Scopus subject areas

  • Biochemistry

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    Smith, L. A., Makarova, A. V., Samson, L., Thiesen, K. E., Dhar, A., & Bessho, T. (2012). Bypass of a psoralen DNA interstrand cross-link by DNA polymerases β, l, and κ in Vitro. Biochemistry, 51(44), 8931-8938. https://doi.org/10.1021/bi3008565