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

Nat Commun. 2020 Sep 25;11(1):4869. doi: 10.1038/s41467-020-18693-1.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Cell Nucleus / metabolism
  • DNA / metabolism*
  • DNA Breaks, Double-Stranded*
  • DNA Repair / physiology*
  • Germ Cells
  • Glycoside Hydrolases / genetics
  • Glycoside Hydrolases / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Poly ADP Ribosylation
  • Poly Adenosine Diphosphate Ribose / metabolism
  • Protein Processing, Post-Translational

Substances

  • Caenorhabditis elegans Proteins
  • Nuclear Proteins
  • SYP-1 protein, C elegans
  • Poly Adenosine Diphosphate Ribose
  • DNA
  • Glycoside Hydrolases
  • poly ADP-ribose glycohydrolase