Journal article
ATM/ATR kinases link the synaptonemal complex and DNA double-strand break repair pathway choice
Current biology, Vol.32(21), pp.4719-4726.e4
09/14/2022
DOI: 10.1016/j.cub.2022.08.081
PMCID: PMC9643613
PMID: 36137547
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.
Details
- Title: Subtitle
- ATM/ATR kinases link the synaptonemal complex and DNA double-strand break repair pathway choice
- Creators
- Laura I Láscarez-Lagunas - Department of Genetics, Blavatnik Institute, Harvard Medical School, 77 Avenue Louis Pasteur, Room 334, Boston, MA 02115, USA.Saravanapriah Nadarajan - Department of Genetics, Blavatnik Institute, Harvard Medical School, 77 Avenue Louis Pasteur, Room 334, Boston, MA 02115, USA.Marina Martinez-Garcia - Department of Genetics, Blavatnik Institute, Harvard Medical School, 77 Avenue Louis Pasteur, Room 334, Boston, MA 02115, USA.Julianna N Quinn - Department of Genetics, Blavatnik Institute, Harvard Medical School, 77 Avenue Louis Pasteur, Room 334, Boston, MA 02115, USA.Elena Todisco - Department of Genetics, Blavatnik Institute, Harvard Medical School, 77 Avenue Louis Pasteur, Room 334, Boston, MA 02115, USA.Tanuj Thakkar - Department of Genetics, Blavatnik Institute, Harvard Medical School, 77 Avenue Louis Pasteur, Room 334, Boston, MA 02115, USA.Elizaveta Berson - Department of Genetics, Blavatnik Institute, Harvard Medical School, 77 Avenue Louis Pasteur, Room 334, Boston, MA 02115, USA.Don Eaford - Department of Genetics, Blavatnik Institute, Harvard Medical School, 77 Avenue Louis Pasteur, Room 334, Boston, MA 02115, USA.Oliver Crawley - MRC London Institute of Medical SciencesAlex Montoya - MRC London Institute of Medical SciencesPeter Faull - MRC London Institute of Medical SciencesNuria Ferrandiz - MRC London Institute of Medical SciencesConsuelo Barroso - MRC London Institute of Medical SciencesSara Labella - McGill UniversityEmily Koury - University of IowaSarit Smolikove - University of IowaMonique Zetka - McGill UniversityEnrique Martinez-Perez - MRC London Institute of Medical SciencesMonica P Colaiácovo - Department of Genetics, Blavatnik Institute, Harvard Medical School, 77 Avenue Louis Pasteur, Room 334, Boston, MA 02115, USA. Electronic address: mcolaiacovo@genetics.med.harvard.edu.
- Resource Type
- Journal article
- Publication Details
- Current biology, Vol.32(21), pp.4719-4726.e4
- DOI
- 10.1016/j.cub.2022.08.081
- PMID
- 36137547
- PMCID
- PMC9643613
- ISSN
- 0960-9822
- eISSN
- 1879-0445
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: R01GM072551; DOI: 10.13039/100019324, name: Virginia Marine Resources Commission; DOI: 10.13039/501100000024, name: Canadian Institutes of Health Research, award: 119468
- Language
- English
- Date published
- 09/14/2022
- Academic Unit
- Biology
- Record Identifier
- 9984297658802771
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