H2AFX and MDC1 promote maintenance of genomic integrity in male germ cells
Testa, Erika. (Università degli Studi di Roma "Tor Vergata". Dipartimento di Biomedicina e Prevenzione)
Nardozi, Daniela (Università degli Studi di Roma "Tor Vergata". Dipartimento di Biomedicina e Prevenzione)
Antinozzi, Cristina (Università degli Studi di Roma "Tor Vergata". Dipartimento di Biomedicina e Prevenzione)
Faieta, Monica (Università degli Studi di Roma "Tor Vergata". Dipartimento di Biomedicina e Prevenzione)
Di Cecca, Stefano (Università degli Studi di Roma "Tor Vergata". Dipartimento di Biomedicina e Prevenzione)
Caggiano, Cinzia (Università degli Studi di Roma "Tor Vergata". Dipartimento di Biomedicina e Prevenzione)
Fukuda, Tomoyuki (Niigata University Graduate School of Medical and Dental Sciences. Department of Cellular Physiology)
Bonanno, Elena (Università degli Studi di Roma "Tor Vergata". Unità di Anatomia patologica)
Zhenkun, Lou (Mayo Clinic. Department of Oncology.)
Maldonado Linares, Andros (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Roig, Ignasi (Ignasi) (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Di Giacomo, Monica (European Molecular Biology Laboratory)
Barchi, Marco (Università degli Studi di Roma "Tor Vergata". Dipartimento di Biomedicina e Prevenzione)

Data:	2018
Resum:	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.
Drets:	Tots els drets reservats.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	H2afx ; Mdc1 ; Crossover ; X-Y ; Meiosis ; Checkpoint
Publicat a:	Journal of Cell Science, Vol. 131, issue 6 (2018) , p. jcs214411, ISSN 1477-9137

DOI: 10.1242/jcs.214411
PMID: 29437857

16 p, 12.4 MB

El registre apareix a les col·leccions:
Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut de Biotecnologia i de Biomedicina (IBB)
Articles > Articles de recerca
Articles > Articles publicats