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

Informace

Projekt nespadá pod Ústav výpočetní techniky, ale pod Lékařskou fakultu. Oficiální stránka projektu je na webu muni.cz.

Kód projektu

GA20-08819S

Období řešení

1/2020 - 12/2022

Investor / Programový rámec / typ projektu

Grantová agentura ČR

Standardní projekty

Fakulta / Pracoviště MU

Lékařská fakulta

Nicola Silva, PhD.

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.

Publikace

Počet publikací: 6

2022

Continuous double-strand break induction and their differential processing sustain chiasma formation during Caenorhabditis elegans meiosis

HICKS Tara TRIVEDI Shalini EPPERT Mikayla BOWMAN Richard TIAN Hui DAFALLA Amna CRAHAN Caroline SMOLIKOVE Sarit SILVA Nicola

Článek v odborném periodiku

Cell Reports, rok: 2022, ročník: 40, vydání: 13, DOI
PARG and BRCA1-BARD1 cooperative function regulates DNA repair pathway choice during gametogenesis

TRIVEDI Shalini BLAŽÍČKOVÁ Jitka SILVA Nicola

Článek v odborném periodiku

Nucleic acids research, rok: 2022, ročník: 50, vydání: 21, DOI
Phosphorylation of HORMA-domain protein HTP-3 at Serine 285 is dispensable for crossover formation

DAS Debabrata TRIVEDI Shalini BLAŽÍČKOVÁ Jitka ARUR Swathi SILVA Nicola

Článek v odborném periodiku

G3-Genes, Genomes, Genetics, rok: 2022, ročník: 12, vydání: 5, DOI
Proline-specific aminopeptidase P prevents replication-associated genome instability

SILVA Nicola CASTELLANO-POZO Maikel MATSUZAKI Kenichiro J. BARROSO Consuelo ROMAN-TRUFERO Monica P. CRAIG Hannah BROOKS Darren P. ISAAC R. Elwyn BOULTON Simon P. MARTINEZ-PEREZ Enrique

Článek v odborném periodiku

PLoS Genetics, rok: 2022, ročník: 18, vydání: 1, DOI

2021

Caenorhabditis elegans RMI2 functional homolog-2 (RMIF-2) and RMI1 (RMH-1) have both overlapping and distinct meiotic functions within the BTR complex

VELKOVA M. SILVA Nicola DELLO STRITTO M. R. SCHLEIFFER A. BARRAUD P. HARTL M. JANTSCH V.

Článek v odborném periodiku

PLoS Genetics, rok: 2021, ročník: 17, vydání: 7, DOI

2020

Poly(ADP-ribose) glycohydrolase coordinates meiotic DNA double-strand break induction and repair independent of its catalytic activity

JANISIW Eva RAICES Marilina BALMIR Fabiola PAULIN Luis F. BAUDRIMONT Antoine VON HAESELER Arndt YANOWITZ Judith L. JANTSCH Verena SILVA Nicola

Článek v odborném periodiku

Nature Communications, rok: 2020, ročník: 11, vydání: 1, DOI