Unknown

Dataset Information

0

Repair of a DNA-protein crosslink by replication-coupled proteolysis.


ABSTRACT: DNA-protein crosslinks (DPCs) are caused by environmental, endogenous, and chemotherapeutic agents and pose a severe threat to genome stability. We use Xenopus egg extracts to recapitulate DPC repair in vitro and show that this process is coupled to DNA replication. A DPC on the leading strand template arrests the replisome by stalling the CMG helicase. The DPC is then degraded on DNA, yielding a peptide-DNA adduct that is bypassed by CMG. The leading strand subsequently resumes synthesis, stalls again at the adduct, and then progresses past the adduct using DNA polymerase ?. A DPC on the lagging strand template only transiently stalls the replisome, but it too is degraded, allowing Okazaki fragment bypass. Our experiments describe a versatile, proteolysis-based mechanism of S phase DPC repair that avoids replication fork collapse.

SUBMITTER: Duxin JP 

PROVIDER: S-EPMC4229047 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

altmetric image

Publications

Repair of a DNA-protein crosslink by replication-coupled proteolysis.

Duxin Julien P JP   Dewar James M JM   Yardimci Hasan H   Walter Johannes C JC  

Cell 20141001 2


DNA-protein crosslinks (DPCs) are caused by environmental, endogenous, and chemotherapeutic agents and pose a severe threat to genome stability. We use Xenopus egg extracts to recapitulate DPC repair in vitro and show that this process is coupled to DNA replication. A DPC on the leading strand template arrests the replisome by stalling the CMG helicase. The DPC is then degraded on DNA, yielding a peptide-DNA adduct that is bypassed by CMG. The leading strand subsequently resumes synthesis, stall  ...[more]

Similar Datasets

| S-EPMC5128727 | biostudies-literature
| S-EPMC2748255 | biostudies-literature
| S-EPMC6375733 | biostudies-literature
| S-EPMC6219452 | biostudies-literature
| S-EPMC8441304 | biostudies-literature
| S-EPMC3890373 | biostudies-literature
| S-EPMC6086610 | biostudies-literature
2016-10-06 | PXD004154 | Pride
2017-03-29 | MSV000080743 | MassIVE
| S-EPMC8219891 | biostudies-literature