| Autor: |
Chandana Peddu, Sufang Zhang, Hong Zhao, Agnes Wong, Ernest Y.C. Lee, Marietta Y.W.T. Lee, Zhongtao Zhang |
| Jazyk: |
angličtina |
| Rok vydání: |
2018 |
| Předmět: |
|
| Zdroj: |
iScience, Vol 6, Iss , Pp 52-67 (2018) |
| Druh dokumentu: |
article |
| ISSN: |
2589-0042 |
| DOI: |
10.1016/j.isci.2018.07.009 |
| Popis: |
Summary: 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. : Biochemistry; Molecular Biology; Molecular Genetics Subject Areas: Biochemistry, Molecular Biology, Molecular Genetics |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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