Mismatch repair protein MSH2 regulates translesion DNA synthesis following exposure of cells to UV radiation

Lingna Lv, Fengli Wang, Xiaolu Ma, Yeran Yang, Zhifeng Wang, Hongmei Liu, Xiaoling Li, Zhenbo Liu, Ting Zhang, Min Huang, Errol C. Friedberg, Tie Shan Tang, Caixia Guo

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Translesion DNA synthesis (TLS) can use specialized DNA polymerases to insert and/or extend nucleotides across lesions, thereby limiting stalled replication fork collapse and the potential for cell death. Recent studies have shown that monoubiquitinated proliferating cell nuclear antigen (PCNA) plays an important role in recruitment of Y-family TLS polymerases to stalled replication forks after DNA damage treatment. To explore the possible roles of other factors that regulate the ultraviolet (UV)-induced assembly of specialized DNA polymerases at arrested replication forks, we performed immunoprecipitation experiments combined with mass spectrometry and established that DNA polymerase kappa (Polκ) can partner with MSH2, an important mismatch repair protein associated with hereditary non-polyposis colorectal cancer. We found that depletion of MSH2 impairs PCNA monoubiquitination and the formation of foci containing Polκ and other TLS polymerases after UV irradiation of cells. Interestingly, expression of MSH2 in Rad18-deficient cells increased UV-induced Polκ and REV1 focus formation without detectable changes in PCNA monoubiquitination, indicating that MSH2 can regulate post-UV focus formation by specialized DNA polymerases in both PCNA monoubiquitination-dependent and-independent fashions. Moreover, we observed that MSH2 can facilitate TLS across cyclobutane pyrimidine dimers photoproducts in living cells, presenting a novel role of MSH2 in post-UV cellular responses.

Original languageEnglish (US)
Pages (from-to)10312-10322
Number of pages11
JournalNucleic acids research
Volume41
Issue number22
DOIs
StatePublished - Dec 2013

ASJC Scopus subject areas

  • Genetics

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    Lv, L., Wang, F., Ma, X., Yang, Y., Wang, Z., Liu, H., Li, X., Liu, Z., Zhang, T., Huang, M., Friedberg, E. C., Tang, T. S., & Guo, C. (2013). Mismatch repair protein MSH2 regulates translesion DNA synthesis following exposure of cells to UV radiation. Nucleic acids research, 41(22), 10312-10322. https://doi.org/10.1093/nar/gkt793