atm promotes the obligate xy crossover and both crossover control and chromosome axis integrity on autosomesatm促进专xy交叉和交叉控制常染色体和染色体轴完整.pdfVIP

ATM Promotes the Obligate XY Crossover and both Crossover Control and Chromosome Axis Integrity on Autosomes Marco Barchi1.¤a, Ignasi Roig2., Monica Di Giacomo2¤b, Dirk G. de Rooij3,4, Scott Keeney2,5*, Maria Jasin1,5* 1 Developmental Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America, 2 Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America, 3 Department of Endocrinology and Metabolism, Faculty of Science, Utrecht University, The Netherlands, 4 Center for Reproductive Medicine, Academic Medical Center, Amsterdam, The Netherlands, 5 Weill Graduate School of Medical Sciences of Cornell University, New York, New York, United States of America Abstract 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 2/ 2 spermatocytes undergo apoptosis at mid-prophase of meiosis I, but Atm 2/ 2 meiotic phenotypes are partially rescued by Spo11 heterozygosity, such that ATM-deficient spermatocytes progress to meiotic metaphase I. Strikingly, Spo11+/ 2 2/ 2 Atm spermatocytes are defective in forming the obligate crossover on the sex chromosomes, even though the XY pair is usual