p53 and TAp63 participate in the recombination-dependent pachytene arrest in mouse spermatocytes

PLoS Genet. 2017 Jun 15;13(6):e1006845. doi: 10.1371/journal.pgen.1006845. eCollection 2017 Jun.


To protect germ cells from genomic instability, surveillance mechanisms ensure meiosis occurs properly. In mammals, spermatocytes that display recombination defects experience a so-called recombination-dependent arrest at the pachytene stage, which relies on the MRE11 complex-ATM-CHK2 pathway responding to unrepaired DNA double-strand breaks (DSBs). Here, we asked if p53 family members-targets of ATM and CHK2-participate in this arrest. We bred double-mutant mice combining a mutation of a member of the p53 family (p53, TAp63, or p73) with a Trip13 mutation. Trip13 deficiency triggers a recombination-dependent response that arrests spermatocytes in pachynema before they have incorporated the testis-specific histone variant H1t into their chromatin. We find that deficiency for either p53 or TAp63, but not p73, allowed spermatocytes to progress further into meiotic prophase despite the presence of numerous unrepaired DSBs. Even so, the double mutant spermatocytes apoptosed at late pachynema because of sex body deficiency; thus p53 and TAp63 are dispensable for arrest caused by sex body defects. These data affirm that recombination-dependent and sex body-deficient arrests occur via genetically separable mechanisms.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Cycle Checkpoints
  • Chromatin / genetics
  • DNA Breaks, Double-Stranded
  • DNA Repair / genetics
  • Histones / genetics
  • Male
  • Meiosis / genetics*
  • Mice
  • Pachytene Stage / genetics
  • Phosphoproteins / genetics*
  • Recombination, Genetic*
  • Spermatocytes / growth & development
  • Spermatocytes / metabolism
  • Testis / growth & development
  • Testis / metabolism
  • Trans-Activators / genetics*
  • Tumor Suppressor Protein p53 / genetics*


  • Chromatin
  • Histones
  • Phosphoproteins
  • Trans-Activators
  • Trp63 protein, mouse
  • Tumor Suppressor Protein p53