Cyclin A1-deficient mice lack histone H3 serine 10 phosphorylation and exhibit altered aurora B dynamics in late prophase of male meiosis.
Male mice lacking cyclin A1 protein are sterile. Their sterility results from an arrest in the meiotic cell cycle of spermatocytes, which we now identify as occurring at late diplotene, immediately before diakinesis. The stage of arrest in cyclin A1-deficient mice is distinct from the arrest seen in spermatocytes that are deficient in its putative catalytic partner Cdk2, which occurs much earlier in pachytene. The arrest in cyclin A1-deficient spermatocytes is also accompanied by an unusual clustering of centromeric heterochromatin. Consistent with a possible defect in the centromeric region, immunofluorescent staining of cyclin A1 protein shows localization in the region of the centromere. Phosphorylation of histone H3 at serine 10 in pericentromeric heterochromatin, which normally occurs in late diplotene, is reduced in spermatocytes from heterozygous Ccna1(+/-) testes and completely absent in spermatocytes with no cyclin A1 protein. Concomitantly, the levels of pericentromeric aurora B kinase, known to phosphorylate histone H3 during meiosis, are partially reduced in spermatocytes from testes of heterozygous mice and further reduced in homozygous null spermatocytes. These data suggest a critical and concentration-dependent function for cyclin A1 in the pericentromeric region in late diplotene of meiosis, perhaps in assembly or function of the passenger protein complex.
Nickerson
Helen D
HD
Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA.
Joshi
Ayesha
A
Wolgemuth
Debra J
DJ
D000818:Animals; D064107:Aurora Kinase B; D064127:Aurora Kinases; D002503:Centromere / Q000648:ultrastructure; D002843:Chromatin / Q000378:metabolism; D002875:Chromosomes / Q000378:metabolism / Q000648:ultrastructure; D019925:Cyclin A / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D056750:Cyclin A1; D006570:Heterochromatin / Q000378:metabolism; D006579:Heterozygote; D006657:Histones / Q000378:metabolism*; D008297:Male; D008540:Meiosis; D051379:Mice; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012694:Serine / Q000737:chemistry*; D013090:Spermatocytes / Q000378:metabolism
C503747:Ccna1 protein, mouse; D002843:Chromatin; D019925:Cyclin A; D056750:Cyclin A1; D006570:Heterochromatin; D006657:Histones; D012694:Serine; C576924:Aurkb protein, mouse; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases