Informace o projektu

Pochopení úlohy PARG při podpoře tvorby a oprav dvouřetězcových zlomů DNA v meióze

Logo poskytovatele
Kód projektu
GA20-08819S
Období řešení
1/2020 - 12/2022
Investor / Programový rámec / typ projektu
Grantová agentura ČR
Fakulta / Pracoviště MU
Lékařská fakulta

ADP-ribosylation is a transient post-translational modification set by PARP1/2 and removed by PARG, which is promptly triggered by DNA damage. PARP1/2 double knock-out or null PARG mutant mice die at early stages of embryonic development preventing their study in the germ cells, where physiological induction of DNA damage is essential to promote faithful chromosome segregation. Caenorhabditis elegans PARP1/2 and PARG null mutants are viable and fertile, allowing the unprecedented analysis of their roles during meiosis. We have collected strong preliminary observations that uncover a previously unknown role for PARG in stimulating meiotic DNA double strand break (DSB) formation and in promoting their homologous recombination-mediated repair together with BRCA1. By exploiting the powerful genetics, biochemical and cytological tools provided by the C. elegans system, we expect to shed new light on how catabolism of ADP-ribose influences DSB induction/repair dynamics in the germ cells and to identify the targets of PARG-1 in vivo, a type of analysis never carried out up to date.