ABSTRACT
Induction and repair of DNA breaks in meiosis ensures faithful chromosome segregation and maintenance of genome integrity. Homologous recombination is the preferred DNA repair system in the gametes and requires BRCA2-dependent loading of the recombinases RAD51-DMC1. Null BRCA2 mutations in mammals are embryonic lethal, which has hindered the study of BRCA2 in the germ line, leaving its roles poorly understood. We generated a functional CRISPR-tagged line of C. elegans brc-2/BRCA2 to isolate interactors in meiotic cells via proteomic approach. We identified the novel factor RIPR-1 and found that has essential roles during meiotic DNA repair by acting in a complex with BRC-2. Through genetics, cell biology and biochemical tools we will dissect the meiotic functions of RIPR-1 and its functional interplay with BRC-2 as well as with FIGL-1/FIGNL1, shown to counteract BRCA2 activity in other organisms and that has remained largely uncharacterized in worms. Our analysis will shed new light on the requirements imposed by RIPR-1-BRC-2-FIGL-1 functions during germ cells development in metazoans.

AIMS
With the proposed research we will:
1) characterization of the phenotypes caused by loss of ripr-1 in oogenesis;
2) analyse the epistatic relationships between ripr-1 and brc-2 during meiotic DNA repair;
3) dissect the functional interplay between RIPR-1-BRC-2-FIGL-1 in regulating RAD-51 dynamics in the germ line.

Cíle udržitelného rozvoje

Masarykova univerzita se hlásí k cílům udržitelného rozvoje OSN, jejichž záměrem je do roku 2030 zlepšit podmínky a kvalitu života na naší planetě.