Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1732, USA.
J Mol Cell Biol. 2011 Jun;3(3):151-8. doi: 10.1093/jmcb/mjq042. Epub 2010 Dec 23.
The DNA damage response (DDR) is a signal transduction pathway that decides the cell's fate either to repair DNA damage or to undergo apoptosis if there is too much damage. Post-translational modifications modulate the assembly and activity of protein complexes during the DDR pathways. MicroRNAs (miRNAs) are emerging as a class of endogenous gene modulators that control protein levels, thereby adding a new layer of regulation to the DDR. In this review, we describe a new role for miRNAs in regulating the cellular response to DNA damage with a focus on DNA double-strand break damage. We also discuss the implications of miRNA's role in the DDR to stem cells, including embryonic stem cells and cancer stem cells, stressing the potential applications for miRNAs to be used as sensitizers for cancer radiotherapy and chemotherapy.
DNA 损伤反应 (DDR) 是一种信号转导通路，它决定了细胞的命运，要么修复 DNA 损伤，要么在损伤过大时发生细胞凋亡。翻译后修饰调节 DDR 途径中蛋白复合物的组装和活性。MicroRNAs（miRNAs）作为一类内源性基因调节剂，可控制蛋白质水平，从而为 DDR 增加了一个新的调控层。在这篇综述中，我们描述了 miRNA 在调节细胞对 DNA 损伤的反应中的新作用，重点是 DNA 双链断裂损伤。我们还讨论了 miRNA 在干细胞（包括胚胎干细胞和癌症干细胞）中的 DDR 中的作用，强调了 miRNA 作为癌症放射治疗和化疗增敏剂的潜在应用。
