Odorisio T, Rodriguez T A, Evans E P, Clarke A R, Burgoyne P S
Laboratory of Developmental Genetics, National Institute for Medical Research, London, UK.
Nat Genet. 1998 Mar;18(3):257-61. doi: 10.1038/ng0398-257.
Evidence is accumulating that meiosis is subject to 'checkpoints' that monitor the quality of this complex process. In yeast, unresolved double strand breaks (DSBs) in DNA are thought to trigger a 'recombination checkpoint' that leads to pachytene arrest. In higher eukaryotes, there is evidence for a checkpoint that monitors chromosome synapsis and in mammals the most compelling evidence relates to the sex chromosomes. In normal male mice, there is synapsis between the X and Y pseudoautosomal regions; in XSxr(a)O mice, with a single asynaptic sex chromosome, there is arrest at the first meiotic metaphase, the arrested cells being eliminated by apoptosis (our unpublished data). Satisfying the requirement for pseudoautosomal synapsis by providing a pairing partner for the XSxr(a) chromosome avoids this arrest. We have considered that this 'synapsis checkpoint' may be a modification of the yeast 'recombination checkpoint' with unresolved DSBs (a corollary of asynapsis) providing the trigger for apoptosis. DSBs induced by irradiation are known to trigger apoptosis in a number of cell types via a p53-dependent pathway, and we now show that irradiation-induced spermatogonial apoptosis is also p53-dependent. In contrast, the apoptotic elimination of spermatocytes with synaptic errors proved to be p53-independent.
越来越多的证据表明，减数分裂受到“检查点”的调控，这些检查点监控着这一复杂过程的质量。在酵母中，DNA中未解决的双链断裂（DSB）被认为会触发一个“重组检查点”，导致粗线期停滞。在高等真核生物中，有证据表明存在一个监控染色体联会的检查点，在哺乳动物中，最有说服力的证据与性染色体有关。在正常雄性小鼠中，X和Y假常染色体区域之间存在联会；在XSxr(a)O小鼠中，由于有一条性染色体未发生联会，在第一次减数分裂中期会出现停滞，停滞的细胞会通过凋亡被清除（我们未发表的数据）。通过为XSxr(a)染色体提供一个配对伙伴来满足假常染色体联会的要求，可以避免这种停滞。我们认为这个“联会检查点”可能是酵母“重组检查点”的一种变体，未解决的DSB（联会失败的一个必然结果）触发了细胞凋亡。已知辐射诱导的DSB会通过p53依赖的途径在多种细胞类型中触发细胞凋亡，我们现在表明辐射诱导的精原细胞凋亡也是p53依赖的。相比之下，具有联会错误的精母细胞的凋亡清除被证明是p53非依赖的。
