Cohesin Causes Replicative DNA Damage by Trapping DNA Topological Stress

DNA 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 complex...

Full description

Saved in:
Bibliographic Details
Published in:Molecular cell Vol. 78; no. 4; p. 739
Main Authors: Minchell, Nicola Elizabeth, Keszthelyi, Andrea, Baxter, Jonathan
Format: Journal Article
Language:English
Published: United States 21.05.2020
Subjects:
Adenosine Triphosphatases - genetics
Adenosine Triphosphatases - metabolism
Cell Cycle Proteins - genetics
Cell Cycle Proteins - metabolism
Chromosomal Proteins, Non-Histone - genetics
Chromosomal Proteins, Non-Histone - metabolism
Chromosomes, Fungal
Cohesins
DNA Damage
DNA Replication
DNA Topoisomerases, Type II - genetics
DNA Topoisomerases, Type II - metabolism
DNA, Fungal - genetics
DNA, Fungal - metabolism
DNA, Ribosomal - genetics
DNA, Ribosomal - metabolism
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Multiprotein Complexes - genetics
Multiprotein Complexes - metabolism
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - metabolism
Saccharomyces cerevisiae Proteins - genetics
Saccharomyces cerevisiae Proteins - metabolism
DNA topology
cohesin
condensin
DNA damage
SMC
topoisomerases
DNA replication stress
ISSN:1097-4164, 1097-4164
Online Access:Get more information
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:DNA 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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1097-4164
1097-4164
DOI:10.1016/j.molcel.2020.03.013