Rockmill Beth, Voelkel-Meiman Karen, Roeder G Shirleen
Howard Hughes Medical Institute, Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06520-8103, USA.
Genetics. 2006 Dec;174(4):1745-54. doi: 10.1534/genetics.106.058933. Epub 2006 Oct 8.
In most organisms, meiotic chromosome segregation is dependent on crossovers (COs), which enable pairs of homologous chromosomes to segregate to opposite poles at meiosis I. In mammals, the majority of meiotic chromosome segregation errors result from a lack of COs between homologs. Observations in Homo sapiens and Drosophila melanogaster have revealed a second class of exceptional events in which a CO occurred near the centromere of the missegregated chromosome. We show that in wild-type strains of Saccharomyces cerevisiae, most spore inviability is due to precocious separation of sister chromatids (PSSC) and that PSSC is often associated with centromere-proximal crossing over. COs, as opposed to nonreciprocal recombination events (NCOs), are preferentially associated with missegregation. Strains mutant for the RecQ homolog, SGS1, display reduced spore viability and increased crossing over. Much of the spore inviability in sgs1 results from PSSC, and these events are often associated with centromere-proximal COs, just as in wild type. When crossing over in sgs1 is reduced by the introduction of a nonnull allele of SPO11, spore viability is improved, suggesting that the increased PSSC is due to increased crossing over. We present a model for PSSC in which a centromere-proximal CO promotes local loss of sister-chromatid cohesion.
在大多数生物体中,减数分裂染色体分离依赖于交叉互换(COs),交叉互换使得同源染色体对在减数第一次分裂时能分离到相对的两极。在哺乳动物中,大多数减数分裂染色体分离错误是由于同源染色体之间缺乏交叉互换。在人类和黑腹果蝇中的观察结果揭示了另一类特殊事件,即在错分离染色体的着丝粒附近发生了交叉互换。我们发现,在酿酒酵母的野生型菌株中,大多数孢子不可育是由于姐妹染色单体过早分离(PSSC),并且PSSC常与着丝粒近端交叉互换相关。与非相互重组事件(NCOs)不同,交叉互换优先与错分离相关。RecQ同源物SGS1的突变菌株表现出孢子活力降低和交叉互换增加。sgs1中许多孢子不可育是由PSSC导致的,并且这些事件常与着丝粒近端交叉互换相关,就像在野生型中一样。当通过引入SPO11的非无效等位基因来减少sgs1中的交叉互换时,孢子活力得到改善,这表明增加的PSSC是由于交叉互换增加所致。我们提出了一个PSSC模型,其中着丝粒近端交叉互换促进了姐妹染色单体凝聚力的局部丧失。