Details:

Alternative Title:
Nucleic Acids Res
Publisher's site:
http://dx.doi.org/10.1093/nar/gku300
Personal Author:
Sarangi, Prabha ; Bartosova, Zdenka ; Altmannova, Veronika ; Holland, Cory ; Chavdarova, Melita ; ... More +
Sarangi, Prabha ; Bartosova, Zdenka ; Altmannova, Veronika ; Holland, Cory ; Chavdarova, Melita ; Lee, Sang Eun ; Krejci, Lumir ; Zhao, Xiaolan Less -
Description:
The Saccharomyces cerevisiae Rad1-Rad10 complex is a conserved, structure-specific endonuclease important for repairing multiple types of DNA lesions. Upon recruitment to lesion sites, Rad1-Rad10 removes damaged sequences, enabling subsequent gap filling and ligation. Acting at mid-steps of repair, the association and dissociation of Rad1-Rad10 with DNA can influence repair efficiency. We show that genotoxin-enhanced Rad1 sumoylation occurs after the nuclease is recruited to lesion sites. A single lysine outside Rad1's nuclease and Rad10-binding domains is sumoylated in vivo and in vitro. Mutation of this site to arginine abolishes Rad1 sumoylation and impairs Rad1-mediated repair at high doses of DNA damage, but sustains the repair of a single double-stranded break. The timing of Rad1 sumoylation and the phenotype bias toward high lesion loads point to a post-incision role for sumoylation, possibly affecting Rad1 dissociation from DNA. Indeed, biochemical examination shows that sumoylation of Rad1 decreases the complex's affinity for DNA without affecting other protein properties. These findings suggest a model whereby sumoylation of Rad1 promotes its disengagement from DNA after nuclease cleavage, allowing it to efficiently attend to large numbers of DNA lesions.
Subjects:
[+]
DNA DNA Damage DNA Repair DNA Repair Enzymes Endonucleases Genome Integrity, Repair And Replication Intracellular Signaling Peptides And Proteins Lysine Mutation Protein-Serine-Threonine Kinases Saccharomyces Cerevisiae Proteins Sumoylation Ubiquitin-Protein Ligases
Source:
Nucleic Acids Res. 2014; 42(10):6393-6404.
Pubmed ID:
24753409
Pubmed Central ID:
PMC4041466
Document Type:
Journal Article
Funding:
GM071011/GM/NIGMS NIH HHS/United States ; GM080670/GM/NIGMS NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R01 GM071011/GM/NIGMS NIH HHS/United States ; R01 GM080670/GM/NIGMS NIH HHS/United States ; ... More +
GM071011/GM/NIGMS NIH HHS/United States ; GM080670/GM/NIGMS NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R01 GM071011/GM/NIGMS NIH HHS/United States ; R01 GM080670/GM/NIGMS NIH HHS/United States ; RSG-12-013-01-CCG/CC/ODCDC CDC HHS/United States Less -
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:fb20da04dbead32a03fd9ddd73c4362008556c66dd4337b8cc37db84b52cf593
Download URL:
https://stacks.cdc.gov/view/cdc/32202/cdc_32202_DS1.pdf
File Type:

Supporting Files

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