Underappreciated Roles of DNA Polymerase δ in Replication Stress Survival.

Jeannette Fuchs, Anais Cheblal, Susan M Gasser

Trends in genetics : TIG 2021 May

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Recent structural analysis of Fe-S centers in replication proteins and insights into the structure and function of DNA polymerase δ (DNA Pol δ) subunits have shed light on the key role played by this polymerase at replication forks under stress. The sequencing of cancer genomes reveals multiple point mutations that compromise the activity of POLD1, the DNA Pol δ catalytic subunit, whereas the loci encoding the accessory subunits POLD2 and POLD3 are amplified in a very high proportion of human tumors. Consistently, DNA Pol δ is key for the survival of replication stress and is involved in multiple long-patch repair pathways. Synthetic lethality arises from compromising the function and availability of the noncatalytic subunits of DNA Pol δ under conditions of replication stress, opening the door to novel therapies. Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.

Citation

Jeannette Fuchs, Anais Cheblal, Susan M Gasser. Underappreciated Roles of DNA Polymerase δ in Replication Stress Survival. Trends in genetics : TIG. 2021 May;37(5):476-487