In somatic cells,H2afxandMdc1are 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 inH2afx -/- spermatocytes, we found that the synapsis of autosomes and X-Y chromosomes was impaired in a relevant fraction of cells. Such defect correlated with an abnormal recombination profile. Conversely,Mdc1was dispensable for the synapsis of the autosomes, and only played a minor role in X-Y synapsis, relatively toH2afxThis 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 thatH2afxandMdc1cooperate 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,H2afxandMdc1promote the maintenance of genome integrity.

Testa, E., Nardozi, D., Antinozzi, C., Faieta, M., Di Cecca, S., Caggiano, C., et al. (2018). H2AFX and MDC1 promote maintenance of genomic integrity in male germ cells. JOURNAL OF CELL SCIENCE, jcs.214411 [10.1242/jcs.214411].

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

TESTA, ERIKA;ANTINOZZI, CRISTINA;FAIETA, MONICA;Bonanno, Elena
Membro del Collaboration Group
;
DI GIACOMO, MONICA;Barchi, Marco
2018

Abstract

In somatic cells,H2afxandMdc1are 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 inH2afx -/- spermatocytes, we found that the synapsis of autosomes and X-Y chromosomes was impaired in a relevant fraction of cells. Such defect correlated with an abnormal recombination profile. Conversely,Mdc1was dispensable for the synapsis of the autosomes, and only played a minor role in X-Y synapsis, relatively toH2afxThis 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 thatH2afxandMdc1cooperate 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,H2afxandMdc1promote the maintenance of genome integrity.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/08 - Anatomia Patologica
English
Checkpoint; Crossover; H2afx; Mdc1; Meiosis; X-Y
Testa, E., Nardozi, D., Antinozzi, C., Faieta, M., Di Cecca, S., Caggiano, C., et al. (2018). H2AFX and MDC1 promote maintenance of genomic integrity in male germ cells. JOURNAL OF CELL SCIENCE, jcs.214411 [10.1242/jcs.214411].
Testa, E; Nardozi, D; Antinozzi, C; Faieta, M; Di Cecca, S; Caggiano, C; Fukuda, T; Bonanno, E; Zhenkun, L; Maldonado, A; Roig, I; DI GIACOMO, M; Barchi, M
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/194133
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