论文
论文标题:Parp1 promotes sleep, which enhances DNA repair in neurons
作者:David Zada, Yaniv Sela, Noa Matosevich, Adir Monsonego, Tali Lerer-Goldshtein, Yuval Nir, Lior Appelbaum
期刊:Molecular Cell
发表时间:2021/11/18
数字识别码:10.1016/j.molcel.2021.10.026
摘要:
The characteristics of the sleep drivers and the mechanisms through which sleep relieves the cellular homeostatic pressure are unclear. In flies, zebrafish, mice, and humans, DNA damage levels increase during wakefulness and decrease during sleep. Here, we show that 6 h of consolidated sleep is sufficient to reduce DNA damage in the zebrafish dorsal pallium. Induction of DNA damage by neuronal activity and mutagens triggered sleep and DNA repair. The activity of the DNA damage response (DDR) proteins Rad52 and Ku80 increased during sleep, and chromosome dynamics enhanced Rad52 activity. The activity of the DDR initiator poly(ADP-ribose) polymerase 1 (Parp1) increased following sleep deprivation. In both larva zebrafish and adult mice, Parp1 promoted sleep. Inhibition of Parp1 activity reduced sleep-dependent chromosome dynamics and repair. These results demonstrate that DNA damage is a homeostatic driver for sleep, and Parp1 pathways can sense this cellular pressure and facilitate sleep and repair activity.
抽象的
细胞暴露于各种内源性和外源性损伤,这些损伤会导致 DNA 损伤,如果未修复,会损害基因组完整性并导致各种疾病的发展,包括癌症。最近的证据表明聚(ADP-核糖)聚合酶 1 (PARP1) 参与各种 DNA 修复途径和维持基因组稳定性。因此,PARP1 的抑制作用在临床上被用于治疗各种癌症,包括 DNA 修复缺陷的卵巢癌、乳腺癌和前列腺癌。了解 PARP1 在维持基因组完整性中的作用不仅对于设计新型化疗药物很重要,而且对于深入了解癌细胞的化疗耐药机制也至关重要。在这篇综述中,我们讨论了 PARP1 在介导 DNA 代谢各个方面的作用