title: Defective cohesin is associated with age-dependent misaligned chromosomes in oocytes.
abstract: Aneuploidy often results from chromosome misalignment at metaphases. Oocytes from senescence-accelerated mice (SAM) exhibit increased chromosome misalignment with age, which originates from nuclear factors. This work sought to further characterize the underlying defects of chromosome misalignments. Using immunofluorescence microscopy with specific antibodies, several specific components associated with spindles or chromosomes, including centrosomes, centromeres and cohesin complex were examined. No obvious differences were found in the distribution of centrosome focus at the spindle pole of oocytes from young and aged SAM, regardless of chromosome alignments, although cytoplasmic centrosome foci were significantly reduced in aged SAM (P < 0.0001). Oocytes from both young and aged SAM exhibited centromere-associated protein-E (CENP-E) at centromeres of all chromosomes, including misaligned chromosomes from aged SAM, demonstrating that CENP-E did not contribute to chromosome misalignments. Notably, both meiotic cohesin proteins located between sister chromatids, REC8 (recombinant 8), STAG3 (stromal antigen 3) and SMC1beta, were remarkably reduced in oocytes from aged SAM. Further, degradation of the cohesin was even more obvious in SAM than in hybrid F1 mice with age, which may explain why SAM are vulnerable to aneuploidy. This natural ageing mouse model shows that defective cohesin coincides with increased incidence of chromosome misalignment and precocious separations of sister chromatids.
authors.affiliation: Department of Obstetrics and Gynecology, University of South Florida College of Medicine, Tampa, Florida 33612, USA. liutelom@yahoo.com
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.forename: David L
authors.initials: DL
authors.lastname: Keefe
mesh_terms: D000375:Aging / Q000235:genetics* / Q000502:physiology; D000782:Aneuploidy; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D002503:Centromere / Q000378:metabolism; D043171:Chromosomal Instability / Q000502:physiology*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D020090:Chromosome Segregation / Q000502:physiology*; D005260:Female; D018386:Kinetochores / Q000502:physiology; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D009865:Oocytes / Q000166:cytology / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D009687:Nuclear Proteins; D010750:Phosphoproteins; D000097722:Cohesins; C465863:Rec8 protein, mouse; C438001:Smc1l2 protein, mouse; C498637:Stag3 protein, mouse; C068688:centromere protein E