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

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Authors

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

Year of publication 2020
Type Article in Periodical
Magazine / Source Nature Communications
MU Faculty or unit

Faculty of Medicine

Citation
Web https://www.nature.com/articles/s41467-020-18693-1.pdf
Doi http://dx.doi.org/10.1038/s41467-020-18693-1
Keywords Poly(ADP-ribose) glycohydrolase; meiotic DNA double-strand break induction
Description Poly(ADP-ribosyl)ation is a reversible post-translational modification synthetized by ADP-ribose transferases and removed by poly(ADP-ribose) glycohydrolase (PARG), which plays important roles in DNA damage repair. While well-studied in somatic tissues, much less is known about poly(ADP-ribosyl)ation in the germline, where DNA double-strand breaks are introduced by a regulated program and repaired by crossover recombination to establish a tether between homologous chromosomes. The interaction between the parental chromosomes is facilitated by meiotic specific adaptation of the chromosome axes and cohesins, and reinforced by the synaptonemal complex. Here, we uncover an unexpected role for PARG in coordinating the induction of meiotic DNA breaks and their homologous recombination-mediated repair in Caenorhabditis elegans. PARG-1/PARG interacts with both axial and central elements of the synaptonemal complex, REC-8/Rec8 and the MRN/X complex. PARG-1 shapes the recombination landscape and reinforces the tightly regulated control of crossover numbers without requiring its catalytic activity. We unravel roles in regulating meiosis, beyond its enzymatic activity in poly(ADP-ribose) catabolism. Poly(ADP-ribose) glycohydrolase (PARG) is involved in different cellular processes including DNA repair. Here the authors reveal a role for PARG in regulating meiotic DNA double strand break induction and repair in Caenorhabditis elegans.
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