Click here to close Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly. We suggest using a current version of Chrome, FireFox, or Safari.
XB-ART-49472
Cell October 9, 2014; 159 (2): 346-57.

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

Duxin JP , Dewar JM , Yardimci H , Walter JC .


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 ζ. 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.

PubMed ID: 25303529
PMC ID: PMC4229047
Article link: Cell
Grant support: [+]

References [+] :
Arias, Replication-dependent destruction of Cdt1 limits DNA replication to a single round per cell cycle in Xenopus egg extracts. 2005, Pubmed, Xenbase


Xenbase: The Xenopus Model Organism Knowledgebase.
Version: 4.16.0
Major funding for Xenbase is provided by grant P41 HD064556