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

Laura I Láscarez-Lagunas; Saravanapriah Nadarajan; Marina Martinez-Garcia; Julianna N Quinn; Elena Todisco; Tanuj Thakkar; Elizaveta Berson; Don Eaford; Oliver Crawley; Alex Montoya; Peter Faull; Nuria Ferrandiz; Consuelo Barroso; Sara Labella; Emily Koury; Sarit Smolikove; Monique Zetka; Enrique Martinez-Perez; Monica P Colaiácovo

doi:10.1016/j.cub.2022.08.081

Back

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

Journal article

Open access

Peer reviewed

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

Laura I Láscarez-Lagunas, Saravanapriah Nadarajan, Marina Martinez-Garcia, Julianna N Quinn, Elena Todisco, Tanuj Thakkar, Elizaveta Berson, Don Eaford, Oliver Crawley, Alex Montoya, …

Current biology, Vol.32(21), pp.4719-4726.e4

09/14/2022

DOI: 10.1016/j.cub.2022.08.081

PMCID: PMC9643613

PMID: 36137547

Files and links (1)

url

https://doi.org/10.1016/j.cub.2022.08.081View

Published (Version of record) Open Access

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 Sciences
Alex Montoya - MRC London Institute of Medical Sciences
Peter Faull - MRC London Institute of Medical Sciences
Nuria Ferrandiz - MRC London Institute of Medical Sciences
Consuelo Barroso - MRC London Institute of Medical Sciences
Sara Labella - McGill University
Emily Koury - University of Iowa
Sarit Smolikove - University of Iowa
Monique Zetka - McGill University
Enrique Martinez-Perez - MRC London Institute of Medical Sciences
Monica 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
NLM abbreviation: Curr Biol
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

Metrics

25 Record Views

16 Times Cited - Web of Science