ATM promotes the obligate XY crossover and both crossover control and chromosome axis integrity on autosomes
Barchi, Marco (Memorial Sloan Kettering Cancer Center)
Roig, Ignasi, (Ignasi) dir. (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Di Giacomo, Monica (Memorial Sloan-Kettering Cancer Center (Nova York, Estats Units d'Amèrica))
De Rooij, Dirk G.. (Utrecht University. Department of Endocrinology and Metabolism (Països Baixos))
Keeney, Scott (Cornell University. Weill Graduate School of Medical Sciences (Nova York, Estats Units d'Amèrica))
Jasin, Maria (Cornell University. Weill Graduate School of Medical Sciences (Nova York, Estats Units d'Amèrica))

Data:	2008
Resum:	During meiosis in most sexually reproducing organisms, recombination forms crossovers between homologous maternal and paternal chromosomes and thereby promotes proper chromosome segregation at the first meiotic division. The number and distribution of crossovers are tightly controlled, but the factors that contribute to this control are poorly understood in most organisms, including mammals. Here we provide evidence that the ATM kinase or protein is essential for proper crossover formation in mouse spermatocytes. ATM deficiency causes multiple phenotypes in humans and mice, including gonadal atrophy. Mouse Atm−/− spermatocytes undergo apoptosis at mid-prophase of meiosis I, but Atm−/− meiotic phenotypes are partially rescued by Spo11 heterozygosity, such that ATM-deficient spermatocytes progress to meiotic metaphase I. Strikingly, Spo11+/−Atm−/− spermatocytes are defective in forming the obligate crossover on the sex chromosomes, even though the XY pair is usually incorporated in a sex body and is transcriptionally inactivated as in normal spermatocytes. The XY crossover defect correlates with the appearance of lagging chromosomes at metaphase I, which may trigger the extensive metaphase apoptosis that is observed in these cells. In addition, control of the number and distribution of crossovers on autosomes appears to be defective in the absence of ATM because there is an increase in the total number of MLH1 foci, which mark the sites of eventual crossover formation, and because interference between MLH1 foci is perturbed. The axes of autosomes exhibit structural defects that correlate with the positions of ongoing recombination. Together, these findings indicate that ATM plays a role in both crossover control and chromosome axis integrity and further suggests that ATM is important for coordinating these features of meiotic chromosome dynamics.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; Versió publicada
Matèria:	Ovaries ; Homologous chromosomes ; Sex chromosomes ; Spermatocytes ; Oocytes ; Metaphase ; Autosomes
Publicat a:	PLoS Genetics, Vol. 4, Issue 5 (May 2008) , p. e1000076, ISSN 1553-7404

DOI: 10.1371/journal.pgen.1000076
PMID: 18497861

17 p, 866.2 KB

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