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Title: Simultaneous disruption of two DNA polymerases, Polη and Polζ, in Avian DT40 cells unmasks the role of Polη in cellular response to various DNA lesions.
Authors: Hirota, Kouji
Sonoda, Eiichiro
Kawamoto, Takuo  kyouindb  KAKEN_id  orcid (unconfirmed)
Motegi, Akira  kyouindb  KAKEN_id
Masutani, Chikahide
Hanaoka, Fumio
Szüts, Dávid
Iwai, Shigenori
Sale, Julian E
Lehmann, Alan
Takeda, Shunichi  kyouindb  KAKEN_id
Author's alias: 武田, 俊一
Issue Date: Oct-2010
Publisher: Public Library of Science
Journal title: PLoS genetics
Volume: 6
Issue: 10
Thesis number: e1001151
Abstract: Replicative DNA polymerases are frequently stalled by DNA lesions. The resulting replication blockage is released by homologous recombination (HR) and translesion DNA synthesis (TLS). TLS employs specialized TLS polymerases to bypass DNA lesions. We provide striking in vivo evidence of the cooperation between DNA polymerase η, which is mutated in the variant form of the cancer predisposition disorder xeroderma pigmentosum (XP-V), and DNA polymerase ζ by generating POLη(-/-)/POLζ(-/-) cells from the chicken DT40 cell line. POLζ(-/-) cells are hypersensitive to a very wide range of DNA damaging agents, whereas XP-V cells exhibit moderate sensitivity to ultraviolet light (UV) only in the presence of caffeine treatment and exhibit no significant sensitivity to any other damaging agents. It is therefore widely believed that Polη plays a very specific role in cellular tolerance to UV-induced DNA damage. The evidence we present challenges this assumption. The phenotypic analysis of POLη(-/-)/POLζ(-/-) cells shows that, unexpectedly, the loss of Polη significantly rescued all mutant phenotypes of POLζ(-/-) cells and results in the restoration of the DNA damage tolerance by a backup pathway including HR. Taken together, Polη contributes to a much wide range of TLS events than had been predicted by the phenotype of XP-V cells.
Rights: © 2010 Hirota et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI(Published Version): 10.1371/journal.pgen.1001151
PubMed ID: 20949111
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