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• W2147054512 startingPage "4473" @default.
• W2147054512 abstract "Unique among translesion synthesis (TLS) DNA polymerases, pol ζ is essential during embryogenesis. To determine whether pol ζ is necessary for proliferation of normal cells, primary mouse fibroblasts were established in which Rev3L could be conditionally inactivated by Cre recombinase. Cells were grown in 2% O 2 to prevent oxidative stress-induced senescence. Cells rapidly became senescent or apoptotic and ceased growth within 3–4 population doublings. Within one population doubling following Rev3L deletion, DNA double-strand breaks and chromatid aberrations were found in 30–50% of cells. These breaks were replication dependent, and found in G1 and G2 phase cells. Double-strand breaks were reduced when cells were treated with the reactive oxygen species scavenger N-acetyl-cysteine, but this did not rescue the cell proliferation defect, indicating that several classes of endogenously formed DNA lesions require Rev3L for tolerance or repair. T-antigen immortalization of cells allowed cell growth. In summary, even in the absence of external challenges to DNA, pol ζ is essential for preventing replication-dependent DNA breaks in every division of normal mammalian cells. Loss of pol ζ in slowly proliferating mouse cells in vivo may allow accumulation of chromosomal aberrations that could lead to tumorigenesis. Pol ζ is unique amongst TLS polymerases for its essential role in cell proliferation." @default.
• W2147054512 created "2016-06-24" @default.
• W2147054512 creator A5019966463 @default.
• W2147054512 creator A5064044884 @default.
• W2147054512 creator A5065003651 @default.
• W2147054512 date "2012-02-07" @default.
• W2147054512 modified "2023-10-16" @default.
• W2147054512 title "DNA polymerase zeta is required for proliferation of normal mammalian cells" @default.
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• W2147054512 doi "https://doi.org/10.1093/nar/gks054" @default.
• W2147054512 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3378892" @default.
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• W2147054512 hasPublicationYear "2012" @default.
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