哺乳动物卵巢储备形成中的DNA损伤修复

DNA Damage and Repair during Ovarian Reserve Formation

在哺乳动物卵巢储备的形成过程中,生殖细胞处于DNA复制、交换和重组的活跃期,对各种内外损伤因素敏感,易发生DNA损伤。多条DNA损伤修复途径在此期间发挥作用。同源重组途径修复DNA双键断裂,保护和重启停滞复制叉;范可尼贫血途径修复链间交联,促进复制叉重启;碱基切除修复途径是全基因组的表观遗传编程的重要机制;错配修复途径维持减数分裂进程,促进重组过程的交叉形成和稳定;核苷酸切除修复途径促进修复链间交联等。这些功能对于维持生殖细胞基因组稳定、减少生殖细胞凋亡、促进生殖细胞增殖和多能性表达以调节原始生殖细胞发育形成卵巢储备至关重要。更好了解哺乳动物卵巢储备形成中的DNA损伤修复,为原发性卵巢功能不全的病因学解析提供理论基础。

In the process of the formation of ovarian reserve,the mammalian germ cells are in the active stage of DNA replication,exchange and recombination.DNA of this stage is sensitive to various internal and external damage factors,so it is predisposed to DNA damage.There are multiple pathways of DNA repair during this period.Homologous recombination(HR)pathway repairs DNA double-strand breaks,protects and restarts the stalled replication forks.Fanconi anemia(FA)pathway repairs interstrand crosslinks and promotes the replication forks to restart.Base excision repair(BER)pathway is an important mechanism of genome-wide epigenetic programming.Mismatch repair(MMR)pathway maintains the meiosis process and promotes the crossover formation and stabilization of the recombination process.Nucleotide excision repair(NER)pathway facilitates the repair of interstrand crosslinks.These pathways are essential for maintaining genomic stability of germ cell,reducing germ cell apoptosis,promoting germ cell proliferation and pluripotency expression to regulate the development of primordial germ cells so as to form ovarian reserve.To understand well the DNA damage and repair during ovarian reserve formation provides a theoretical basis for the etiological analysis of primary ovarian insufficiency(POI).