A natural meiotic DNA break site in Schizosaccharomyces pombe is a hotspot of gene conversion, highly associated with crossing over

A natural meiotic DNA break site in Schizosaccharomyces pombe is a hotspot of gene conversion, highly associated with crossing over
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DOI:
10.1534/genetics.104.037176
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发表时间:
2005-02-01
期刊:
影响因子:
3.3
通讯作者:
Smith, GR
Smith, GR
中科院分区:
生物学2区
文献类型:
--
作者:
Cromie, GA;Rubio, CA;Smith, GR

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在粟酒裂殖酵母中,在显著但广泛分离的位点观察到启动重组的减数分裂特异性DNA断裂。我们研究了这些位点之一,染色体I上的mbs 1位点的断裂和重组之间的关系。对应于10%的染色单体的断裂被映射到分布在2.1 kb区域的四个簇。簇内标记的基因转换发生在11%的四分体中(3%的减数分裂染色单体),使mbs 1与其他分裂酵母标记相比成为转换热点。大约80%的这些转换与交叉的侧翼标记,这表明一个强大的偏见,在减数分裂断裂修复对一代的交叉。在其他三个基因座(ade 6、ade 7和ura 1)的转换事件中也观察到了这种偏倚。在mbs 1侧翼的90 kb区域中观察到的所有交换中,总共有50-80%发生在包含断裂位点的4.8 kb间隔内。因此,mbs 1也是交换的热点,mbs 1的断裂产生了90 kb区间内的大多数交换。Rec 12(Spo 11直系同源物)和I-SceI诱导的mbs 1处的断裂都与> 25 kb的明显无断裂间隔中的交换无关。讨论了在这种无中断间隔中产生交叉的可能机制。
In Schizosaccharomyces pombe, meiosis-specific DNA breaks that initiate recombination are observed at prominent but widely separated sites. We investigated the relationship between breakage and recombination at one of these sites, the mbs1 locus on chromosome I. Breaks corresponding to 10% of chromatids were mapped to four clusters spread over a 2.1-kb region. Gene conversion of markers within the clusters occurred in 11% of tetrads (3% of meiotic chromatids), making mbs1 a conversion hotspot when compared to other fission yeast markers. Approximately 80% of these conversions were associated with crossing over of flanking markers, suggesting a strong bias in meiotic break repair toward the generation of crossovers. This bias was observed in conversion events at three other loci, ade6, ade7, and ura1. A total of 50-80% of all crossovers seen in a 90-kb region flanking mbs1 occurred in a 4.8-kb interval containing the break sites. Thus, mbs1 is also a hotspot of crossing over, with breakage at mbs1 generating most of the crossovers in the 90-kb interval. Neither Rec12 (Spo11 ortholog) nor I-SceI-induced breakage at mbs1 was significantly associated with crossing over in an apparently break-free interval > 25 kb away. Possible mechanisms for generating crossovers in such break-free intervals are discussed.