PT  - JOURNAL ARTICLE
AU  - Erika Testa
AU  - Daniela Nardozi
AU  - Cristina Antinozzi
AU  - Monica Faieta
AU  - Stefano Di Cecca
AU  - Cinzia Caggiano
AU  - Tomoyuki Fukuda
AU  - Elena Bonanno
AU  - Lou Zenkun
AU  - Andros Maldonado
AU  - Ignasi Roig
AU  - Monica Di Giacomo
AU  - Marco Barchi
TI  - H2AFX and MDC1 Protect Genomic Integrity in Male Germ Cells by Promoting Recombination and Activation of the Recombination-Dependent Checkpoint
AID  - 10.1101/235085
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 235085
4099  - http://biorxiv.org/content/early/2017/12/15/235085.short
4100  - http://biorxiv.org/content/early/2017/12/15/235085.full
AB  - 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 synapsis of the autosomes and X-Y chromosomes were impaired in a relevant fraction of cells. Such defect correlated with an abnormal recombination profile. Conversely, Mdc1 was dispensable for the synapsis of the autosomes, and only played a minor role in X-Y synapsis, relatively to 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 showed 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 showed that, in male germ cells, H2afx and Mdc1 promote the maintenance of genome integrity.