Interdependent and separable functions of Caenorhabditis elegans MRN-C complex members couple formation and repair of meiotic DSBs

• DOI: 10.1073/pnas.1719029115
• Publication Date: 2018-04-23T19:13:56Z
• Authors: Chloe Girard; Baptiste Roelens; Karl A. Zawadzki; Anne M. Villeneuve
• Keywords: 0301 basic medicine; Meiosis; 03 medical and health sciences; DNA End-Joining Repair; Embryo, Nonmammalian; Animals; DNA Breaks, Double-Stranded; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Homologous Recombination

Significance

Double-strand breaks (DSBs) are deleterious DNA lesions, and impairment of the DSB repair machinery can lead to devastating diseases, such as Nijmegen Breakage Syndrome (NBS). During meiosis, DSBs represent a “necessary evil”: they are required to promote formation of crossovers between homologous chromosomes. Crossovers, in turn, ensure correct chromosome inheritance during gamete formation, which is essential for viability and normal development of embryos. During meiosis, numerous DSBs are actively created, so meiotic cells must ensure that all breaks are properly repaired to ensure crossover formation and restore genomic integrity. Here, we identify Caenorhabditis elegans NBS-1 as essential to properly process meiotic DSBs to both promote crossover formation and antagonize an error-prone DSB repair pathway, thereby ensuring faithful chromosome inheritance.