Functional Interplay between the 53BP1-Ortholog Rad9 and the Mre11 Complex Regulates Resection, End-Tethering and Repair of a Double-Strand Break
570
DNA End-Joining Repair
Saccharomyces cerevisiae Proteins
anzsrc-for: 0604 Genetics
DNA, Single-Stranded
Cell Cycle Proteins
Saccharomyces cerevisiae
QH426-470
3101 Biochemistry and Cell Biology
Double-Stranded
03 medical and health sciences
Single-Stranded
Genetics
2.1 Biological and endogenous factors
DNA Breaks, Double-Stranded
anzsrc-for: 31 Biological Sciences
Homologous Recombination
0303 health sciences
Endodeoxyribonucleases
RecQ Helicases
DNA Breaks
anzsrc-for: 3101 Biochemistry and Cell Biology
DNA
Endonucleases
Rad52 DNA Repair and Recombination Protein
DNA-Binding Proteins
anzsrc-for: 3105 Genetics
Exodeoxyribonucleases
Mutation
Generic health relevance
31 Biological Sciences
Research Article
DOI:
10.1371/journal.pgen.1004928
Publication Date:
2015-01-08T19:20:23Z
AUTHORS (10)
ABSTRACT
The Mre11-Rad50-Xrs2 nuclease complex, together with Sae2, initiates the 5'-to-3' resection of Double-Strand DNA Breaks (DSBs). Extended 3' single stranded DNA filaments can be exposed from a DSB through the redundant activities of the Exo1 nuclease and the Dna2 nuclease with the Sgs1 helicase. In the absence of Sae2, Mre11 binding to a DSB is prolonged, the two DNA ends cannot be kept tethered, and the DSB is not efficiently repaired. Here we show that deletion of the yeast 53BP1-ortholog RAD9 reduces Mre11 binding to a DSB, leading to Rad52 recruitment and efficient DSB end-tethering, through an Sgs1-dependent mechanism. As a consequence, deletion of RAD9 restores DSB repair either in absence of Sae2 or in presence of a nuclease defective MRX complex. We propose that, in cells lacking Sae2, Rad9/53BP1 contributes to keep Mre11 bound to a persistent DSB, protecting it from extensive DNA end resection, which may lead to potentially deleterious DNA deletions and genome rearrangements.
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CITATIONS (106)
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