title: Self-organization of meiotic recombination initiation: general principles and molecular pathways.
abstract: Recombination in meiosis is a fascinating case study for the coordination of chromosomal duplication, repair, and segregation with each other and with progression through a cell-division cycle. Meiotic recombination initiates with formation of developmentally programmed DNA double-strand breaks (DSBs) at many places across the genome. DSBs are important for successful meiosis but are also dangerous lesions that can mutate or kill, so cells ensure that DSBs are made only at the right times, places, and amounts. This review examines the complex web of pathways that accomplish this control. We explore how chromosome breakage is integrated with meiotic progression and how feedback mechanisms spatially pattern DSB formation and make it homeostatic, robust, and error correcting. Common regulatory themes recur in different organisms or in different contexts in the same organism. We review this evolutionary and mechanistic conservation but also highlight where control modules have diverged. The framework that emerges helps explain how meiotic chromosomes behave as a self-organizing system.
authors.affiliation: Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065; email: s-keeney@ski.mskcc.org.
authors.forename: Scott
authors.initials: S
authors.lastname: Keeney
authors.forename: Julian
authors.initials: J
authors.lastname: Lange
authors.forename: Neeman
authors.initials: N
authors.lastname: Mohibullah
mesh_terms: D020090:Chromosome Segregation; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D004706:Endodeoxyribonucleases / Q000235:genetics; D059765:Homologous Recombination / Q000235:genetics*; D008540:Meiosis / Q000235:genetics*; D012441:Saccharomyces cerevisiae
chemical_list: D004268:DNA-Binding Proteins; D004706:Endodeoxyribonucleases
keywords: ATM; DNA double-strand breaks; DNA replication; Spo11; cell cycle