DNA polymerases beta and lambda mediate overlapping and independent roles in base excision repair in mouse embryonic fibroblasts
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Samson-2011-DNA Polymerases.pdf
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Author(s)
Braithwaite, Elena K.
Kedar, Padmini S.
Stumpo, Deborah J.
Bertocci, Barbara
Freedman, Jonathan H.
Samson, Leona D.
Wilson, Samuel H.
Date Issued
August 2010
Journal
PLoS ONE
Publisher
Public Library of Science
Citation
Braithwaite, Elena K. et al. “DNA Polymerases β and λ Mediate Overlapping and Independent Roles in Base Excision Repair in Mouse Embryonic Fibroblasts.” Ed. Janine Santos. PLoS ONE 5 (2010): e12229. Web. 19 Oct. 2011.
Version
Final published version
Abstract
Base excision repair (BER) is a DNA repair pathway designed to correct small base lesions in genomic DNA. While DNA polymerase beta (pol β) is known to be the main polymerase in the BER pathway, various studies have implicated other DNA polymerases in back-up roles. One such polymerase, DNA polymerase lambda (pol λ), was shown to be important in BER of oxidative DNA damage. To further explore roles of the X-family DNA polymerases λ and β in BER, we prepared a mouse embryonic fibroblast cell line with deletions in the genes for both pol β and pol λ. Neutral red viability assays demonstrated that pol λ and pol β double null cells were hypersensitive to alkylating and oxidizing DNA damaging agents. In vitro BER assays revealed a modest contribution of pol λ to single-nucleotide BER of base lesions. Additionally, using co-immunoprecipitation experiments with purified enzymes and whole cell extracts, we found that both pol λ and pol β interact with the upstream DNA glycosylases for repair of alkylated and oxidized DNA bases. Such interactions could be important in coordinating roles of these polymerases during BER.
MIT Department
Massachusetts Institute of Technology. Center for Environmental Health Sciences
Massachusetts Institute of Technology. Department of Biological Engineering
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Creative Commons Attribution
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DOI of Published Version
https://doi.org/10.1371/journal.pone.0012229
