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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
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نویسنده
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hirota k. ,sonoda e. ,kawamoto t. ,motegi a. ,masutani c. ,hanaoka f. ,szüts d. ,iwai s. ,sale j.e. ,lehmann a. ,takeda s.
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منبع
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plos genetics - 2010 - دوره : 6 - شماره : 10 - صفحه:1 -13
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چکیده
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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 polg 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 polg 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. © 2010 hirota et al.
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آدرس
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crest research project,japan science and technology,radiation genetics,graduate school of medicine,kyoto university,kyoto, Japan, crest research project,japan science and technology,radiation genetics,graduate school of medicine,kyoto university,kyoto, Japan, crest research project,japan science and technology,radiation genetics,graduate school of medicine,kyoto university,kyoto, Japan, crest research project,japan science and technology,radiation genetics,graduate school of medicine,kyoto university,kyoto, Japan, solution-oriented research for science and technology (sorst),japan science and technology agency,graduate school of frontier biosciences,osaka university,osaka, Japan, solution-oriented research for science and technology (sorst),japan science and technology agency,graduate school of frontier biosciences,osaka university,osaka,japan,department of life science,faculty of science,gakushuin university,tokyo, Japan, st.george's university of london,london, United Kingdom, division of chemistry,graduate school of engineering science,osaka university,osaka, Japan, medical research council laboratory of molecular biology,cambridge, United Kingdom, genome damage and stability centre,university of sussex,brighton, United Kingdom, crest research project,japan science and technology,radiation genetics,graduate school of medicine,kyoto university,kyoto, Japan
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Authors
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