Regulatory control of DNA end resection by Sae2 phosphorylation

被引：0
作者：
Elda Cannavo
Dominic Johnson
Sara N. Andres
Vera M. Kissling
Julia K. Reinert
Valerie Garcia
Dorothy A. Erie
Daniel Hess
Nicolas H. Thomä
Radoslav I. Enchev
Matthias Peter
R. Scott Williams
Matt J. Neale
Petr Cejka
机构：
[1] Università della Svizzera italiana (USI),Faculty of Biomedical Sciences, Institute for Research in Biomedicine
[2] University of Sussex,Genome Damage and Stability Centre, School of Life Sciences
[3] US National Institutes of Health,Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, Department of Health and Human Services
[4] Eidgenössische Technische Hochschule (ETH),Department of Biology, Institute of Biochemistry
[5] Friedrich Miescher Institute for Biomedical Research,Department of Chemistry, Lineberger Comprehensive Cancer Center
[6] University of Basel,Michael G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences
[7] University of North Carolina,Centre de Recherche en Cancérologie de Marseille (CRCM)
[8] McMaster University,undefined
[9] Institut Paoli Calmettes,undefined
[10] Inserm UMR1068,undefined
[11] CNRS UMR7258,undefined
[12] Aix Marseille Université,undefined
来源：
Nature Communications | / 9卷
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摘要：
DNA end resection plays a critical function in DNA double-strand break repair pathway choice. Resected DNA ends are refractory to end-joining mechanisms and are instead channeled to homology-directed repair. Using biochemical, genetic, and imaging methods, we show that phosphorylation of Saccharomyces cerevisiae Sae2 controls its capacity to promote the Mre11-Rad50-Xrs2 (MRX) nuclease to initiate resection of blocked DNA ends by at least two distinct mechanisms. First, DNA damage and cell cycle-dependent phosphorylation leads to Sae2 tetramerization. Second, and independently, phosphorylation of the conserved C-terminal domain of Sae2 is a prerequisite for its physical interaction with Rad50, which is also crucial to promote the MRX endonuclease. The lack of this interaction explains the phenotype of rad50S mutants defective in the processing of Spo11-bound DNA ends during meiotic recombination. Our results define how phosphorylation controls the initiation of DNA end resection and therefore the choice between the key DNA double-strand break repair mechanisms.
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