title: Homeostatic regulation of meiotic DSB formation by ATM/ATR.
abstract: Ataxia-telangiectasia mutated (ATM) and RAD3-related (ATR) are widely known as being central players in the mitotic DNA damage response (DDR), mounting responses to DNA double-strand breaks (DSBs) and single-stranded DNA (ssDNA) respectively. The DDR signalling cascade couples cell cycle control to damage-sensing and repair processes in order to prevent untimely cell cycle progression while damage still persists [1]. Both ATM/ATR are, however, also emerging as essential factors in the process of meiosis; a specialised cell cycle programme responsible for the formation of haploid gametes via two sequential nuclear divisions. Central to achieving accurate meiotic chromosome segregation is the introduction of numerous DSBs spread across the genome by the evolutionarily conserved enzyme, Spo11. This review seeks to explore and address how cells utilise ATM/ATR pathways to regulate Spo11-DSB formation, establish DSB homeostasis and ensure meiosis is completed unperturbed.
authors.affiliation: Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Brighton BN1 9RQ, UK.
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Cooper
authors.affiliation: Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Brighton BN1 9RQ, UK.
authors.forename: Kayleigh
authors.initials: K
authors.lastname: Wardell
authors.affiliation: Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Brighton BN1 9RQ, UK.
authors.forename: Valerie
authors.initials: V
authors.lastname: Garcia
authors.affiliation: Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Brighton BN1 9RQ, UK. Electronic address: m.neale@sussex.ac.uk.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Neale
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology; D053903:DNA Breaks, Double-Stranded; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D008540:Meiosis / Q000502:physiology*
chemical_list: C576897:Atr protein, mouse; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins
keywords: ATM; ATR; Mec1; Meiosis; Recombination; Spo11; Tel1