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Cohesin causes replicative DNA damage by trapping DNA topological stress
journal contribution
posted on 2023-06-09, 21:03 authored by Nicola Elizabeth Minchell, Andrea KeszthelyiAndrea Keszthelyi, Jon BaxterJon BaxterDNA topological stress inhibits DNA replication fork (RF) progression and contributes to DNA replication stress. In Saccharomyces cerevisiae, we demonstrate that centromeric DNA and the rDNA array are especially vulnerable to DNA topological stress during replication. The activity of the SMC complexes cohesin and condensin are linked to both the generation and repair of DNA topological-stress-linked damage in these regions. At cohesin-enriched centromeres, cohesin activity causes the accumulation of DNA damage, RF rotation, and pre-catenation, confirming that cohesin-dependent DNA topological stress impacts on normal replication progression. In contrast, at the rDNA, cohesin and condensin activity inhibit the repair of damage caused by DNA topological stress. We propose that, as well as generally acting to ensure faithful genetic inheritance, SMCs can disrupt genome stability by trapping DNA topological stress.
Funding
Investigating how replication fork rotation causes chromosomal instability during S phase; G1903; BBSRC-BIOTECHNOLOGY & BIOLOGICAL SCIENCES RESEARCH COUNCIL; BB/N007344/1
History
Publication status
- Published
File Version
- Published version
Journal
Molecular cellISSN
1097-2765Publisher
Cell PressExternal DOI
Issue
4Volume
78Page range
739-751Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
Research groups affiliated with
- Genome Damage and Stability Centre Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2020-04-15First Open Access (FOA) Date
2020-04-15First Compliant Deposit (FCD) Date
2020-04-08Usage metrics
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