Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Biol Reprod. 2010 May;82(5):1000-7. doi: 10.1095/biolreprod.109.080697. Epub 2010 Jan 27.
Poly(ADP-ribosyl)ation is a posttranslational protein modification carried out by a family of enzymes referred to as poly(ADP-ribose) polymerases (PARPs). It has been proposed that the broad nuclear distribution of PARPs may allow them to modulate gene expression in addition to their more accepted role as DNA repair mediators. The role of poly(ADP-ribosyl)ation during oogenesis and folliculogenesis is unknown. Here we found that when 3- to 4-wk-old mice were injected with 5-amninoisoquinolinone, a water soluble inhibitor of poly(ADP-ribosyl)ation, it leads to considerably increased oocyte numbers and a dramatic increase in primordial follicle numbers. Furthermore, we show that inhibition of poly(ADP-ribosyl)ation leads to an increased expression of specific genes and pathways in mouse ovaries, in particular, transforming growth factor superfamily members. Our results demonstrate that poly(ADP-ribosyl)ation, is important in oogenesis and folliculogenesis, and it may have a differential role in regulating gene expression, DNA repair, and apoptosis. The novel function of poly(ADP-ribosyl)ation in oogenesis and folliculogenesis sheds light on the alternative role that DNA repair mediators may play in cellular development and differentiation.
聚（ADP-核糖）化是一种由多聚（ADP-核糖）聚合酶（PARPs）家族的酶进行的翻译后蛋白质修饰。有人提出，PARPs 的广泛核分布可能使它们能够调节基因表达，除了它们更被接受的作为 DNA 修复介质的作用。聚（ADP-核糖）化在卵母细胞发生和卵泡发生中的作用尚不清楚。在这里，我们发现当 3-4 周龄的小鼠注射水溶性聚（ADP-核糖）化抑制剂 5-氨基异喹啉酮时，它会导致卵母细胞数量显著增加，并使原始卵泡数量急剧增加。此外，我们表明，聚（ADP-核糖）化的抑制导致在小鼠卵巢中特定基因和途径的表达增加，特别是转化生长因子超家族成员。我们的结果表明，聚（ADP-核糖）化在卵母细胞发生和卵泡发生中很重要，它可能在调节基因表达、DNA 修复和细胞凋亡方面具有不同的作用。聚（ADP-核糖）化在卵母细胞发生和卵泡发生中的新功能揭示了 DNA 修复介质在细胞发育和分化中可能发挥的替代作用。
