H2AFX and MDC1 promote maintenance of genomic integrity in male germ cells

Erika Testa, Daniela Nardozi, Cristina Antinozzi, Monica Faieta, Stefano Di Cecca, Cinzia Caggiano, Tomoyuki Fukuda, Elena Bonanno, Lou Zhenkun, Andros Maldonado, Ignasi Roig, Monica Di Giacomo, Marco Barchi

Research output: Contribution to journalReview articlepeer-review

10 Scopus citations


In somatic cells, H2afx and Mdc1 are close functional partners in DNA repair and damage response. However, it is not known whether they are also involved in the maintenance of genome integrity in meiosis. By analyzing chromosome dynamics in H2afx-/- spermatocytes, we found that the synapsis of autosomes and X-Y chromosomes was impaired in a fraction of cells. Such defects correlated with an abnormal recombination profile. Conversely, Mdc1 was dispensable for the synapsis of the autosomes and played only a minor role in X-Y synapsis, compared with the action of H2afx. This suggested that those genes have non-overlapping functions in chromosome synapsis. However, we observed that both genes play a similar role in the assembly of MLH3 onto chromosomes, a key step in crossover formation. Moreover, we show that H2afx and Mdc1 cooperate in promoting the activation of the recombination-dependent checkpoint, a mechanism that restrains the differentiation of cells with unrepaired DSBs. This occurs by a mechanism that involves P53. Overall, our data show that, in male germ cells, H2afx and Mdc1 promote the maintenance of genome integrity.

Original languageEnglish (US)
Article numberjcs214411
JournalJournal of cell science
Issue number6
StatePublished - Mar 1 2018


  • Checkpoint
  • Crossover
  • H2afx
  • Mdc1
  • Meiosis
  • X-Y

ASJC Scopus subject areas

  • Cell Biology


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