School of Biological Sciences and Center for Cell and Genome Sciences, University of Utah, Salt Lake City, UT, USA.
School of Biological Sciences and Center for Cell and Genome Sciences, University of Utah, Salt Lake City, UT, USA
Life Sci Alliance. 2023 Jan 25;6(4). doi: 10.26508/lsa.202301906. Print 2023 Apr.
During meiosis, programmed double-strand DNA breaks are repaired to form exchanges between the parental chromosomes called crossovers. Chromosomes lacking a crossover fail to segregate accurately into the gametes, leading to aneuploidy. In addition to engaging the homolog, crossover formation requires the promotion of exchanges, rather than non-exchanges, as repair products. However, the mechanism underlying this meiosis-specific preference is not fully understood. Here, we study the regulation of meiotic sister chromatid exchanges in by direct visualization. We find that a conserved chromosomal interface that promotes exchanges between the parental chromosomes, the synaptonemal complex, can also promote exchanges between the sister chromatids. In both cases, exchanges depend on the recruitment of the same set of pro-exchange factors to repair sites. Surprisingly, although the synaptonemal complex usually assembles between the two DNA molecules undergoing an exchange, its activity does not rely on a specific chromosome conformation. This suggests that the synaptonemal complex regulates exchanges-both crossovers and sister exchanges-by establishing a nuclear domain conducive to nearby recruitment of exchange-promoting factors.
在减数分裂过程中,程序性的双链 DNA 断裂被修复,形成称为交叉的亲本染色体之间的交换。缺乏交叉的染色体不能准确地分离到配子中,导致非整倍体。除了涉及同源染色体外,交叉形成还需要促进交换,而不是非交换作为修复产物。然而,这种减数分裂特异性偏好的机制尚不完全清楚。在这里,我们通过直接可视化研究了 中减数分裂姐妹染色单体交换的调节。我们发现,一个保守的染色体界面可以促进亲本染色体之间的交换,这个界面称为联会复合体,也可以促进姐妹染色单体之间的交换。在这两种情况下,交换都依赖于相同的一组促进交换的因子被招募到修复位点。令人惊讶的是,尽管联会复合体通常在经历交换的两个 DNA 分子之间组装,但它的活性并不依赖于特定的染色体构象。这表明联会复合体通过建立一个有利于附近招募促进交换因子的核域来调节交换——包括交叉和姐妹交换。