Multi-polar mitosis is strongly linked with aggressive cancers and it is a histological diagnostic of tumor-grade. However, factors that cause chromosomes to segregate to more than two spindle poles are not well understood. Here we show that cohesins Rad21, Smc1 and Smc3 are required for bipolar mitosis in human cells. After Rad21 depletion, chromosomes align at the metaphase plate and bipolar spindles assemble in most cases, but in anaphase the separated chromatids segregate to multiple poles. Time-lapse microscopy revealed that the spindle poles often become split in Rad21-depleted metaphase cells. Interestingly, exogenous expression of non-cleavable Rad21 results in multi-polar anaphase. Since cohesins are present at the spindle poles in mitosis, these data are consistent with a non-chromosomal function of cohesin.
We have examined the effects of ageing on the increase in apoptotic cells numbers in the male genital tract of the house mouse (Mus musculus). We have found that not all organs have the same response. There is an induction of apoptosis in both the epididymis and ventral prostate. However, seminal vesicles and other prostatic lobes remain unaffected. Apoptosis was assessed by several methods: TUNEL, detection of the active fragment of caspase-3 and the pattern of DNA fragmentation on agarose gels. This increase in apoptosis is related to the fall in testosterone levels, although there is only a partial decrease in androgen receptor (AR). AR is still present in all tissues and only moderately reduced in the epididymis and ventral prostate. A more intense increase of lipofuscin granules, which may be indicative of oxidative stress, occurred in these tissues. Finally, testosterone supplementation reverses the changes (both in apoptosis and lipofuscin content in the tissue), suggesting a role of androgens in these processes.
By means of silver staining procedures of light microscopy the characteristics of the nucleolus and the NO Rs have been investigated in meiocytes of different grasshopper species. Our results show that: (1) Two is the most common number of chromosomes per haploid genome carrying active NORs although this number may vary from one up to five; (2) NOR activity is preferentially located on medium and short chromosomes but the X and the megameric chromosome are involved in nucleolar organization in a high proportion of the species studied; (3) The NOR location is normally restricted to one end in acro-telocentrics and to the short arm, near the centromere region, in metacentrics; (4) A marked correlation is observed between the number of nucleoli present in the spermatogonial cells and in the first meiotic prophase of a given species; (5) In some cases, the nucleoli are associated to chromosomes during spermatogonial premetaphases.
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