RRC ID |
76215
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Author |
Láscarez-Lagunas LI, Nadarajan S, Martinez-Garcia M, Quinn JN, Todisco E, Thakkar T, Berson E, Eaford D, Crawley O, Montoya A, Faull P, Ferrandiz N, Barroso C, Labella S, Koury E, Smolikove S, Zetka M, Martinez-Perez E, Colaiácovo MP.
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Title |
ATM/ATR kinases link the synaptonemal complex and DNA double-strand break repair pathway choice.
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Journal |
Curr Biol
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Abstract |
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.1,2 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).3,4,5,6,7,8,9 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.
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Volume |
32(21)
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Pages |
4719-4726.e4
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Published |
2022-11-7
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DOI |
10.1016/j.cub.2022.08.081
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PII |
S0960-9822(22)01403-8
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PMID |
36137547
|
PMC |
PMC9643613
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MeSH |
Animals
Caenorhabditis elegans / genetics
Caenorhabditis elegans / metabolism
Caenorhabditis elegans Proteins* / genetics
Caenorhabditis elegans Proteins* / metabolism
DNA / metabolism
DNA Breaks, Double-Stranded*
DNA Repair
Meiosis
Nuclear Proteins / metabolism
Synaptonemal Complex / genetics
Synaptonemal Complex / metabolism
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Resource |
C.elegans |
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