Cytological studies of human meiosis: sex-specific differences in recombination originate at, or prior to, establishment of double-strand breaks.
Cytological studies of human meiosis: sex-specific differences in recombination originate at, or prior to, establishment of double-strand breaks.
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DOI：
10.1371/journal.pone.0085075
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Hassold T
中科院分区：
文献类型：
--
作者：
Gruhn JR;Rubio C;Broman KW;Hunt PA;Hassold T
在包括人类在内的大多数哺乳动物物种中，减数分裂重组是性二态的，但雄性：雌性差异的基础仍然不清楚。在本研究中，我们使用细胞学方法直接比较人类男性和女性之间的重组水平，并检查可能的性别特异性差异的上游事件的双链断裂（DSB）的形成和突触启动。具体而言，我们利用DNA错配修复蛋白MLH 1作为重组事件的标记，RecA同源物RAD 51作为DSB的替代物，以及联会复合物蛋白SYCP 3和/或SYCP 1来检查同源物之间的突触。与连锁研究一致，全基因组重组水平在女性中高于男性，并且交换的位置在性别之间变化。DSB和突触起始位点的后续分析表明，类似的男性：女性的差异，提供了强有力的证据，性别特异性的重组率的差异，建立在减数分裂DSB的形成或之前。然后，我们询问这些差异是否可能与减数分裂轴和/或轴相关DNA的组织变化有关，事实上，我们观察到显着的男性：女性联会复合体（SC）长度和DNA环大小的差异。两者合计，我们的观察结果表明，性别特异性差异在人类重组可能来自染色质的差异之前建立的重组途径的发病。
Meiotic recombination is sexually dimorphic in most mammalian species, including humans, but the basis for the male:female differences remains unclear. In the present study, we used cytological methodology to directly compare recombination levels between human males and females, and to examine possible sex-specific differences in upstream events of double-strand break (DSB) formation and synaptic initiation. Specifically, we utilized the DNA mismatch repair protein MLH1 as a marker of recombination events, the RecA homologue RAD51 as a surrogate for DSBs, and the synaptonemal complex proteins SYCP3 and/or SYCP1 to examine synapsis between homologs. Consistent with linkage studies, genome-wide recombination levels were higher in females than in males, and the placement of exchanges varied between the sexes. Subsequent analyses of DSBs and synaptic initiation sites indicated similar male:female differences, providing strong evidence that sex-specific differences in recombination rates are established at or before the formation of meiotic DSBs. We then asked whether these differences might be linked to variation in the organization of the meiotic axis and/or axis-associated DNA and, indeed, we observed striking male:female differences in synaptonemal complex (SC) length and DNA loop size. Taken together, our observations suggest that sex specific differences in recombination in humans may derive from chromatin differences established prior to the onset of the recombination pathway.
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影响因子：
4.5
作者：
Cheng EY;Hunt PA;Naluai-Cecchini TA;Fligner CL;Fujimoto VY;Pasternack TL;Schwartz JM;Steinauer JE;Woodruff TJ;Cherry SM;Hansen TA;Vallente RU;Broman KW;Hassold TJ
通讯作者：
Hassold TJ
影响因子：
4.5
作者：
Holloway JK;Booth J;Edelmann W;McGowan CH;Cohen PE
通讯作者：
Cohen PE
DOI：
10.1073/pnas.1207854109
发表时间：
2012-10-23
影响因子：
11.1
作者：
Hunt, Patricia A.;Lawson, Crystal;VandeVoort, Catherine A.
通讯作者：
VandeVoort, Catherine A.
DOI：
10.1073/pnas.1212955109
发表时间：
2012-10-02
影响因子：
11.1
作者：
Colome-Tatche, Maria;Cortijo, Sandra;Johannes, Frank
通讯作者：
Johannes, Frank
影响因子：
3.7
作者：
Fledel-Alon A;Leffler EM;Guan Y;Stephens M;Coop G;Przeworski M
通讯作者：
Przeworski M