Cannavo, Elda, Johnson, Dominic, Andres, Sara, Kissling, Vera, Reinert, Julia, Garcia, Valerie, Erie, Dorothy, Hess, Daniel, Thomä, Nicolas, Enchev, Radoslav, Peter, Matthias, Williams, Scott, Neale, Matt and Cejka, Petr (2018) Regulatory control of DNA end resection by Sae2 phosphorylation. Nature Communications, 9. p. 4016. ISSN 2041-1723

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Abstract

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.

Item Type:	Article
Schools and Departments:	School of Life Sciences > Sussex Centre for Genome Damage and Stability
Research Centres and Groups:	Genome Damage and Stability Centre
Related URLs:	https://www.ncbi.nlm.nih.gov/pmc/article...
Depositing User:	Matt Neale
Date Deposited:	17 May 2019 10:19
Last Modified:	01 Jul 2019 15:01
URI:	http://sro.sussex.ac.uk/id/eprint/83823

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