K_Hirota_et_al_2010.pdf (2.14 MB)
Simultaneous disruption of two DNA polymerases, Pol? and Pol?, in Avian DT40 cells unmasks the role of Pol? in cellular response to various DNA lesions
journal contribution
posted on 2023-06-07, 15:35 authored by Kouji Hirota, Eiichiro Sonoda, Takuo Kawamoto, Akira Motegi, Chikahide Masutani, Fumio Hanaoka, Dávid Szüts, Shigenori Iwai, Julian E Sale, Alan LehmannAlan Lehmann, Shunichi TakedaReplicative 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 ?, which is mutated in the variant form of the cancer predisposition disorder xeroderma pigmentosum (XP-V), and DNA polymerase ? by generating POL?-/-/POL?-/- cells from the chicken DT40 cell line. POL?-/- 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 Pol? plays a very specific role in cellular tolerance to UV-induced DNA damage. The evidence we present challenges this assumption. The phenotypic analysis of POL?-/-/POL?-/- cells shows that, unexpectedly, the loss of Pol? significantly rescued all mutant phenotypes of POL?-/- cells and results in the restoration of the DNA damage tolerance by a backup pathway including HR. Taken together, Pol? contributes to a much wide range of TLS events than had been predicted by the phenotype of XP-V cells.
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Publication status
- Published
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- Published version
Journal
PLoS GeneticsISSN
1553-7390Publisher
Public Library of ScienceExternal DOI
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10Volume
6Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
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GDSC332Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2010-11-04First Open Access (FOA) Date
2017-12-01First Compliant Deposit (FCD) Date
2019-07-02Usage metrics
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