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How to fix DNA-protein crosslinks.

Authors
  • Kühbacher, Ulrike1
  • Duxin, Julien P2
  • 1 The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark. , (Denmark)
  • 2 The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark. Electronic address: [email protected] , (Denmark)
Type
Published Article
Journal
DNA repair
Publication Date
Oct 01, 2020
Volume
94
Pages
102924–102924
Identifiers
DOI: 10.1016/j.dnarep.2020.102924
PMID: 32683310
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Proteins that act on DNA, or are in close proximity to it, can become inadvertently crosslinked to DNA and form highly toxic lesions, known as DNA-protein crosslinks (DPCs). DPCs are generated by different chemotherapeutics, environmental or endogenous sources of crosslinking agents, or by lesions on DNA that stall the catalytic cycle of certain DNA processing enzymes. These bulky adducts impair processes on DNA such as DNA replication or transcription, and therefore pose a serious threat to genome integrity. The large diversity of DPCs suggests that there is more than one canonical mechanism to repair them. Indeed, many different enzymes have been shown to act on DPCs by either processing the protein, the DNA or the crosslink itself. In addition, the cell cycle stage or cell type are likely to dictate pathway choice. In recent years, a detailed understanding of DPC repair during S phase has started to emerge. Here, we review the current knowledge on the mechanisms of replication-coupled DPC repair, and describe and also speculate on possible pathways that remove DPCs outside of S phase. Moreover, we highlight a recent paradigm shifting finding that indicates that DPCs are not always detrimental, but can also play a protective role, preserving the genome from more deleterious forms of DNA damage. Copyright © 2020. Published by Elsevier B.V.

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