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Phosphorylation Alters the Properties of Pol η: Implications for Translesion Synthesis.
Peddu, Chandana; Zhang, Sufang; Zhao, Hong; Wong, Agnes; Lee, Ernest Y C; Lee, Marietta Y W T; Zhang, Zhongtao.
Afiliação
  • Peddu C; Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA.
  • Zhang S; Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA.
  • Zhao H; Department of Pathology, New York Medical College, Valhalla, NY 10595, USA.
  • Wong A; Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA.
  • Lee EYC; Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA.
  • Lee MYWT; Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA.
  • Zhang Z; Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA. Electronic address: zhongtao_zhang@nymc.edu.
iScience ; 6: 52-67, 2018 Aug 31.
Article em En | MEDLINE | ID: mdl-30240625
ABSTRACT
There are significant ambiguities regarding how DNA polymerase η is recruited to DNA lesion sites in stressed cells while avoiding normal replication forks in non-stressed cells. Even less is known about the mechanisms responsible for Pol η-induced mutations in cancer genomes. We show that there are two safeguards to prevent Pol η from adventitious participation in normal DNA replication. These include sequestration by a partner protein and low basal activity. Upon cellular UV irradiation, phosphorylation enables Pol η to be released from sequestration by PDIP38 and activates its polymerase function through increased affinity toward monoubiquitinated proliferating cell nuclear antigen (Ub-PCNA). Moreover, the high-affinity binding of phosphorylated Pol η to Ub-PCNA limits its subsequent displacement by Pol δ. Consequently, activated Pol η replicates DNA beyond the lesion site and potentially introduces clusters of mutations due to its low fidelity. This mechanism could account for the prevalence of Pol η signatures in cancer genome.
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Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Risk_factors_studies Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Risk_factors_studies Idioma: En Ano de publicação: 2018 Tipo de documento: Article