Székvölgyi Lóránt, Ohta Kunihiro, Nicolas Alain
Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary.
Department of Life Sciences, The University of Tokyo, 113-8654 Tokyo, Japan.
Cold Spring Harb Perspect Biol. 2015 May 1;7(5):a016527. doi: 10.1101/cshperspect.a016527.
Meiotic recombination is initiated by the formation of DNA double-strand breaks (DSBs) catalyzed by the evolutionary conserved Spo11 protein and accessory factors. DSBs are nonrandomly distributed along the chromosomes displaying a significant (~400-fold) variation of frequencies, which ultimately establishes local and long-range "hot" and "cold" domains for recombination initiation. This remarkable patterning is set up within the chromatin context, involving multiple layers of biochemical activity. Predisposed chromatin accessibility, but also a range of transcription factors, chromatin remodelers, and histone modifiers likely promote local recruitment of DSB proteins, as well as mobilization, sliding, and eviction of nucleosomes before and after the occurrence of meiotic DSBs. Here, we assess our understanding of meiotic DSB formation and methods to change its patterning. We also synthesize current heterogeneous knowledge on how histone modifications and chromatin remodeling may impact this decisive step in meiotic recombination.
减数分裂重组由进化保守的Spo11蛋白及辅助因子催化形成DNA双链断裂(DSB)引发。DSB沿染色体非随机分布,频率呈现显著(约400倍)变化,最终为重组起始建立局部和远距离的“热点”和“冷点”区域。这种显著的模式是在染色质环境中建立的,涉及多层生化活动。易接近的染色质,以及一系列转录因子、染色质重塑因子和组蛋白修饰因子,可能促进DSB蛋白的局部招募,以及减数分裂DSB发生前后核小体的移动、滑动和驱逐。在此,我们评估了我们对减数分裂DSB形成的理解以及改变其模式的方法。我们还综合了当前关于组蛋白修饰和染色质重塑如何影响减数分裂重组这一决定性步骤的不同知识。