ATM/ATR kinases link the synaptonemal complex and DNA double-strand break repair pathway choice

DNA double-strand breaks (DSBs) are deleterious lesions, which must be repaired precisely to maintain genomic stability. During meiosis, programmed DSBs are repaired via homologous recombination (HR) while repair using the nonhomologous end joining (NHEJ) pathway is inhibited, thereby ensuring crossover formation and accurate chromosome segregation. 1 Ranjha L. Howard S.M. Cejka P. Main steps in DNA double-strand break repair: an introduction to homologous recombination and related processes. Chromosoma. 2018; 127: 187-214 Crossref PubMed Scopus (199) Google Scholar ,2 Clejan I. Boerckel J. Ahmed S. Developmental modulation of nonhomologous end joining in Caenorhabditis elegans. Genetics. 2006; 173: 1301-1317 Crossref PubMed Scopus (87) Google Scholar How DSB repair pathway choice is implemented during meiosis is unknown. In C. elegans, meiotic DSB repair takes place in the context of the fully formed, highly dynamic zipper-like structure present between homologous chromosomes called the synaptonemal complex (SC). 3 Colaiácovo M.P. MacQueen A.J. Martinez-Perez E. McDonald K. Adamo A. La Volpe A. Villeneuve A.M. Synaptonemal complex assembly in C. elegans is dispensable for loading strand-exchange proteins but critical for proper completion of recombination. Dev. Cell. 2003; 5: 463-474 Abstract Full Text Full Text PDF PubMed Scopus (317) Google Scholar ,4 Couteau F. Zetka M. DNA damage during meiosis induces chromatin remodeling and synaptonemal complex disassembly. Dev. Cell. 2011; 20: 353-363 Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar ,5 Voelkel-Meiman K. Moustafa S.S. Lefrançois P. Villeneuve A.M. MacQueen A.J. Full-length synaptonemal complex grows continuously during meiotic prophase in budding yeast. PLoS Genet. 2012; 8e1002993 Crossref PubMed Scopus (51) Google Scholar ,6 Machovina T.S. Mainpal R. Daryabeigi A. McGovern O. Paouneskou D. Labella S. Zetka M. Jantsch V. Yanowitz J.L. A surveillance system ensures crossover formation in C. elegans. Curr. Biol. 2016; 26: 2873-2884 Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar ,7 Rog O. Köhler S. Dernburg A.F. The synaptonemal complex has liquid crystalline properties and spatially regulates meiotic recombination factors. eLife. 2017; 6e21455 Crossref PubMed Scopus (122) Google Scholar ,8 Nadarajan S. Lambert T.J. Altendorfer E. Gao J. Blower M.D. Waters J.C. Colaiácovo M.P. Polo-like kinase-dependent phosphorylation of the synaptonemal complex protein SYP-4 regulates double-strand break formation through a negative feedback loop. eLife. 2017; 6e23437 Crossref PubMed Scopus (50) Google Scholar ,9 Pattabiraman D. Roelens B. Woglar A. Villeneuve A.M. Meiotic recombination modulates the structure and dynamics of the synaptonemal complex during C. elegans meiosis. PLoS Genet. 2017; 13e1006670 Crossref PubMed Scopus (61) Google Scholar The SC consists of a pair of lateral elements bridged by a central region composed of the SYP proteins in C. elegans. How the structural components of the SC are regulated to maintain the architectural integrity of the assembled SC around DSB repair sites remained unclear. Here, we show that SYP-4, a central region component of the SC, is phosphorylated at Serine 447 in a manner dependent on DSBs and the ATM/ATR DNA damage response kinases. We show that this SYP-4 phosphorylation is critical for preserving the SC structure following exogenous (γ-IR-induced) DSB formation and for promoting normal DSB repair progression and crossover patterning following SPO-11-dependent and exogenous DSBs. We propose a model in which ATM/ATR-dependent phosphorylation of SYP-4 at the S447 site plays important roles both in maintaining the architectural integrity of the SC following DSB formation and in warding off repair via the NHEJ repair pathway, thereby preventing aneuploidy.