DNA交联修复是减数分裂前生殖细胞发育过程中基因组稳定性的保障，这一成果由剑桥大学分子生物学MRC实验室Gerry P. Crossan小组取得。 2019年8月出版的《自然—遗传学》发表了这项成果。

研究小组为生殖系中DNA链间交叉修复定义了一个基本角色。这个修复过程是对胚胎发育成熟时期的原始生殖细胞十分重要。失活的交联修复会导致基因的不稳定性，这种不稳定性只限于很窄的时间窗口中生殖嵴内的原始生殖细胞。在成功激活原始生殖细胞的转录程序之后,一个强有力的质量控制机制检测和驱动受损的原始生殖细胞凋亡。因此,这些发现定义了一种DNA损伤的来源和随后在生殖细胞中DNA修复反应的本质,这确保了基因组世代传播的忠实性。

研究人员表示，种系重新突变是进化多样性的基础，也是遗传疾病的基础。然而,分子起源、生殖系突变的机制和时间还没有十分清楚。

附：英文原文

Title: DNA cross-link repair safeguards genomic stability during premeiotic germ cell development

Author: Ross J. Hill, Gerry P. Crossan

Issue&Volume: Volume 51 Issue 8

Abstract: Germline de novo mutations are the basis of evolutionary diversity but also of genetic disease. However, the molecular origin, mechanisms and timing of germline mutagenesis are not fully understood. Here, we define a fundamental role for DNA interstrand cross-link repair in the germline. This repair process is essential for primordial germ cell (PGC) maturation during embryonic development. Inactivation of cross-link repair leads to genetic instability that is restricted to PGCs within the genital ridge during a narrow temporal window. Having successfully activated the PGC transcriptional program, a potent quality control mechanism detects and drives damaged PGCs into apoptosis. Therefore, these findings define a source of DNA damage and the nature of the subsequent DNA repair response in germ cells, which ensures faithful transmission of the genome between generations.

DOI: 10.1038/s41588-019-0471-2

Source:https://www.nature.com/articles/s41588-019-0471-2