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Repair of a DNA-protein crosslink by replication-coupled proteolysis.
- Source :
-
Cell [Cell] 2014 Oct 09; Vol. 159 (2), pp. 346-57. - Publication Year :
- 2014
-
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 ΞΆ. 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.<br /> (Copyright © 2014 Elsevier Inc. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1097-4172
- Volume :
- 159
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cell
- Publication Type :
- Academic Journal
- Accession number :
- 25303529
- Full Text :
- https://doi.org/10.1016/j.cell.2014.09.024