Project information
Pochopení úlohy PARG při podpoře tvorby a oprav dvouřetězcových zlomů DNA v meióze
- Project Identification
- GA20-08819S
- Project Period
- 1/2020 - 12/2022
- Investor / Pogramme / Project type
-
Czech Science Foundation
- Standard Projects
- MU Faculty or unit
- Faculty of Medicine
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.
Publications
Total number of publications: 6
2022
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Continuous double-strand break induction and their differential processing sustain chiasma formation during Caenorhabditis elegans meiosis
Cell Reports, year: 2022, volume: 40, edition: 13, DOI
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PARG and BRCA1-BARD1 cooperative function regulates DNA repair pathway choice during gametogenesis
Nucleic acids research, year: 2022, volume: 50, edition: 21, DOI
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Phosphorylation of HORMA-domain protein HTP-3 at Serine 285 is dispensable for crossover formation
G3-Genes, Genomes, Genetics, year: 2022, volume: 12, edition: 5, DOI
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Proline-specific aminopeptidase P prevents replication-associated genome instability
PLoS Genetics, year: 2022, volume: 18, edition: 1, DOI
2021
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Caenorhabditis elegans RMI2 functional homolog-2 (RMIF-2) and RMI1 (RMH-1) have both overlapping and distinct meiotic functions within the BTR complex
PLoS Genetics, year: 2021, volume: 17, edition: 7, DOI
2020
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Poly(ADP-ribose) glycohydrolase coordinates meiotic DNA double-strand break induction and repair independent of its catalytic activity
Nature Communications, year: 2020, volume: 11, edition: 1, DOI