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

Eva Janisiw, Marilina Raices, Fabiola Balmir, Luis F. Paulin, Antoine Baudrimont, Arndt Haeseler, Judith L. Yanowitz, Verena Jantsch and Nicola Silva ()
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Eva Janisiw: University of Vienna
Marilina Raices: University of Pittsburgh School of Medicine
Fabiola Balmir: University of Pittsburgh School of Medicine
Luis F. Paulin: University of Vienna
Antoine Baudrimont: University of Vienna
Arndt Haeseler: University of Vienna
Judith L. Yanowitz: University of Pittsburgh School of Medicine
Verena Jantsch: University of Vienna
Nicola Silva: Masaryk University

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-020-18693-1

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