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Current Biology
Article . 2012
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SUMOylation of the α-Kleisin Subunit of Cohesin Is Required for DNA Damage-Induced Cohesion

Authors: McAleenan, Alexandra; Cordon-Preciado, Violeta; Clemente-Blanco, Andres; Liu, I-Chun; Sen, Nicholas; Leonard, Joanne; Jarmuz, Adam; +1 Authors

SUMOylation of the α-Kleisin Subunit of Cohesin Is Required for DNA Damage-Induced Cohesion

Abstract

Cohesion between sister chromatids is fundamental to ensure faithful chromosome segregation during mitosis and accurate repair of DNA damage postreplication. At the molecular level, cohesion establishment involves two defined events, a chromatin binding step and a chromatid entrapment event driven by posttranslational modifications on cohesin subunits.Here, we show that modification by the small ubiquitin-like protein (SUMO) is required for sister chromatid tethering after DNA damage. We find that all subunits of cohesin become SUMOylated upon exposure to DNA damaging agents or presence of a DNA double-strand break. We have mapped all lysine residues on cohesin's α-kleisin subunit Mcd1 (Scc1) where SUMO can conjugate. We demonstrate that Mcd1 SUMOylation-deficient alleles are still recruited to DSB-proximal regions but are defective in tethering sister chromatids and consequently fail to establish damage-induced cohesion both at DSBs and undamaged chromosomes. Moreover, we demonstrate that the bulk of Mcd1 SUMOylation in response to damage is carried out by the SUMO E3 ligase Nse2, a subunit of the related Smc5-Smc6 complex. SUMOylation occurs in cells with compromised Chk1 kinase activity, necessary for known posttranslational modifications on Mcd1, required for damage-induced cohesion.These findings demonstrate that SUMOylation of Mcd1 is a novel prerequisite for the establishment of DNA damage-induced cohesion at DSB-proximal regions and cohesion-associating regions (CARs) genome-wide.

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Keywords

Saccharomyces cerevisiae Proteins, Agricultural and Biological Sciences(all), Biochemistry, Genetics and Molecular Biology(all), Chromosomal Proteins, Non-Histone, Sumoylation, Cell Cycle Proteins, Saccharomyces cerevisiae, Chromatids, Chromosome Segregation, DNA Breaks, Double-Stranded, Cohesins, DNA Damage

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
65
Top 10%
Top 10%
Top 10%
hybrid