Underappreciated Roles of DNA Polymerase δ in Replication Stress Survival

被引：35

作者：

Fuchs, Jeannette ^{[1
]}

Cheblal, Anais ^{[1
,2
]}

Gasser, Susan M. ^{[1
,2
]}

机构：

[1] Friedrich Miescher Inst Biomed Res, Maulbeerstr 66, CH-4058 Basel, Switzerland

[2] Univ Basel, Fac Sci, Klingelbergstr 90, CH-4056 Basel, Switzerland

来源：

TRENDS IN GENETICS | 2021年 / 37卷 / 05期

关键词：

ONCOGENE-INDUCED SENESCENCE; BREAK-INDUCED REPLICATION; DAMAGE RESPONSE; RIBONUCLEOTIDE REDUCTASE; GENOMIC INSTABILITY; GERMLINE MUTATIONS; CATALYTIC SUBUNIT; ACTIVE-SITE; POLD1; GENE; CANCER;

D O I：

10.1016/j.tig.2020.12.003

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Recent structural analysis of Fe-S centers in replication proteins and insights into the structure and function of DNA polymerase 5 (DNA Pol 5) 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 5 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 5 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 5 under conditions of replication stress, opening the door to novel therapies.

引用

页码：476 / 487

页数：12

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