Department of Biomedicine and Prevention, Section of Anatomy, University of Rome Tor Vergata, 00133 Rome, Italy.
Department of Cellular Physiology, Niigata University Graduate School of Medical and Dental Sciences, 951-8510 Niigata, Japan.
J Cell Sci. 2018 Mar 20;131(6):jcs214411. doi: 10.1242/jcs.214411.
In somatic cells, and are close functional partners in DNA repair and damage response. However, it is not known whether they are also involved in the maintenance of genome integrity in meiosis. By analyzing chromosome dynamics in spermatocytes, we found that the synapsis of autosomes and X-Y chromosomes was impaired in a fraction of cells. Such defects correlated with an abnormal recombination profile. Conversely, was dispensable for the synapsis of the autosomes and played only a minor role in X-Y synapsis, compared with the action of This suggested that those genes have non-overlapping functions in chromosome synapsis. However, we observed that both genes play a similar role in the assembly of MLH3 onto chromosomes, a key step in crossover formation. Moreover, we show that and cooperate in promoting the activation of the recombination-dependent checkpoint, a mechanism that restrains the differentiation of cells with unrepaired DSBs. This occurs by a mechanism that involves P53. Overall, our data show that, in male germ cells, and promote the maintenance of genome integrity.This article has an associated First Person interview with the first author of the paper.
在体细胞中， 和 在 DNA 修复和损伤反应中是紧密的功能伙伴。然而，它们是否也参与减数分裂中基因组完整性的维持尚不清楚。通过分析 精母细胞中的染色体动力学，我们发现部分细胞中常染色体和 X-Y 染色体的联会受到损害。这种缺陷与异常的重组谱相关。相反，与 的作用相比， 对于常染色体的联会是可有可无的，而在 X-Y 联会中只起次要作用，这表明这些基因在染色体联会中有非重叠的功能。然而，我们观察到这两个基因在 MLH3 组装到染色体上的过程中发挥着相似的作用，这是形成交叉的关键步骤。此外，我们还表明， 和 合作促进了依赖重组的检查点的激活，这是一种抑制未修复 DSBs 的细胞分化的机制。这是通过一种涉及 P53 的机制发生的。总的来说，我们的数据表明，在男性生殖细胞中， 和 促进基因组完整性的维持。本文有该论文第一作者的相关第一人称采访。
