The role of CSM3, MRC1, and TOF1 in minisatellite stability and large loop DNA repair during meiosis in yeast.
The role of CSM3, MRC1, and TOF1 in minisatellite stability and large loop DNA repair during meiosis in yeast.
复制标题
DOI：
10.1016/j.fgb.2012.10.007
复制
发表时间：
2013-01
影响因子：
3
通讯作者：
Kirkpatrick, David T.
中科院分区：
文献类型：
--
作者：
LeClere, Andrea R.;Yang, John K.;Kirkpatrick, David T.
酿酒酵母减数分裂重组过程中的双链断裂 (DSB) 修复导致异源双链 DNA 的形成，这是一种由来自两条同源染色体的单链组成的杂合 DNA 分子。异源双链 DNA 内链之间的序列差异会产生错配或大的不配对环，这些都是修复的底物。至少有两条途径可以修复异源双链 DNA 内形成的大环：RAD1 依赖性大环修复 (LLR) 途径和另一个尚未表征的 RAD1 独立性 LLR 途径。减数分裂重组过程中大环的修复对于称为小卫星的重复 DNA 序列的基因组稳定性尤其重要。小卫星 DNA 束在有丝分裂细胞分裂期间通常是稳定的，但在减数分裂期间长度经常发生变化。使用酵母小卫星系统，其中与 HRAS1 原癌基因相关的人类小卫星已插入酿酒酵母 HIS4 上游的重组热点区域，我们的实验室之前表明，RAD1 依赖性 LLR 途径控制小卫星长度扩张，但不控制收缩。在这里，我们表明小卫星长度扩张是由 CSM3 和 TOF1 基因的产物控制的，而收缩是由 MRC1 控制的。通过检查 26bp his4-lopd 插入杂合酵母菌株的减数分裂分离模式，我们发现删除 CSM3 会导致 LLR 活性丧失，类似于 RAD1 突变体中所见的情况。双突变体分析表明，删除 RAD1 和 CSM3 后，修复环的失败会加剧——特别是填充环的修复类型，这会产生小卫星长度扩展。提出了基于这些结果的小卫星长度改变模型。
Double-stranded break (DSB) repair during meiotic recombination in yeast Saccharomyces cerevisiae leads to the formation of heteroduplex DNA, a hybrid DNA molecule composed of single strands from two homologous chromosomes. Differences in sequence between the strands within heteroduplex DNA generate mismatches or large unpaired loops that are substrates for repair. At least two pathways function to repair large loops that form within heteroduplex DNA: the RAD1-dependent large loop repair (LLR) pathway and another as yet uncharacterized RAD1-independent LLR pathway. Repair of large loops during meiotic recombination is especially important for the genomic stability of the repetitive DNA sequences known as minisatellites. Minisatellite DNA tracts are generally stable during mitotic cell divisions but frequently alter in length during meiosis. Using a yeast minisatellite system in which the human minisatellite associated with the HRAS1 proto-oncogene has been inserted into the recombination hotspot region upstream of HIS4 in S. cerevisiae, our lab previously showed that the RAD1-dependent LLR pathway controls minisatellite length expansions, but not contractions. Here we show that minisatellite length expansions are controlled by the products of the CSM3 and TOF1 genes, while contractions are controlled by MRC1. By examining meiotic segregation patterns in yeast strains heterozygous for the 26bp his4-lopd insert, we found that deleting CSM3 caused a loss of LLR activity similar to that seen in a RAD1 mutant. Double mutant analysis revealed that failure to repair loops is exacerbated upon deleting both RAD1 and CSM3 - specifically the type of repair that fills in loops, which would generate minisatellite length expansions. A model for minisatellite length alteration based on these results is presented.
登录
查看更多内容
影响因子：
10.5
作者：
Fricke, WM;Brill, SJ
通讯作者：
Brill, SJ
影响因子：
64.5
作者：
Fekairi S;Scaglione S;Chahwan C;Taylor ER;Tissier A;Coulon S;Dong MQ;Ruse C;Yates JR 3rd;Russell P;Fuchs RP;McGowan CH;Gaillard PHL
通讯作者：
Gaillard PHL
影响因子：
158.5
作者：
KRONTIRIS, TG;DEVLIN, B;RISCH, N
通讯作者：
RISCH, N
影响因子：
3.3
作者：
Maloisel, L;Bhargava, J;Roeder, GS
通讯作者：
Roeder, GS
影响因子：
64.8
作者：
Kirkpatrick, DT;Petes, TD
通讯作者：
Petes, TD