NYMC Faculty Publications
Journal Title
iScience
First Page
52
Last Page
67
Document Type
Article
Publication Date
8-1-2018
Department
Pathology, Microbiology and Immunology
Second Department
Biochemistry and Molecular Biology
Abstract
There are significant ambiguities regarding how DNA polymerase eta 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 eta-induced mutations in cancer genomes. We show that there are two safeguards to prevent Pol eta 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 eta 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 eta to Ub-PCNA limits its subsequent displacement by Pol delta. Consequently, activated Pol eta 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 eta signatures in cancer genome.
Recommended Citation
Peddu, C., Zhang, S., Zhao, H., Wong, A., Lee, E., Lee, M., & Zhang, Z. (2018). Phosphorylation Alters the Properties of Pol eta: Implications for Translesion Synthesis. iScience, 6, 52-67. https://doi.org/10.1016/j.isci.2018.07.009
Publisher's Statement
Originally published in iScience, 6, 52-67. The original material can be found here.
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
