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...

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Vydané v:	Molecular cell Ročník 78; číslo 4; s. 739
Hlavní autori:	Minchell, Nicola Elizabeth, Keszthelyi, Andrea, Baxter, Jonathan
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States 21.05.2020
Predmet:	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
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Popis
Shrnutí:	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.
Bibliografia:	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