Bao Yunhe, Shen Xuetong
Department of Carcinogenesis, Science Park Research Division, MD Anderson Cancer Center, Smithville, TX 78957, USA.
Curr Opin Genet Dev. 2007 Apr;17(2):126-31. doi: 10.1016/j.gde.2007.02.010. Epub 2007 Feb 22.
ATP-dependent chromatin remodeling complexes use ATP hydrolysis to remodel nucleosomes and have well-established functions in transcription. However, emerging lines of evidence suggest that chromatin remodeling complexes are important players in DNA double-strand break (DSB) repair as well. The INO80 and SWI2 subfamilies of chromatin remodeling complexes have been found to be recruited to the double-strand lesions and to function directly in both homologous recombination and non-homologous end-joining, the two major conserved DSB repair pathways. Improperly repaired DSBs are implicated in cancer development in higher organisms. Understanding how chromatin remodeling complexes contribute to DSB repair should provide new insights into the mechanisms of carcinogenesis and might suggest new targets for cancer treatment.
ATP 依赖的染色质重塑复合体利用 ATP 水解来重塑核小体,并在转录过程中具有既定的功能。然而,越来越多的证据表明,染色质重塑复合体在 DNA 双链断裂(DSB)修复中也是重要的参与者。已发现染色质重塑复合体的 INO80 和 SWI2 亚家族会被招募到双链损伤部位,并在同源重组和非同源末端连接这两种主要的保守 DSB 修复途径中直接发挥作用。在高等生物中,修复不当的 DSB 与癌症发展有关。了解染色质重塑复合体如何促进 DSB 修复,应为癌变机制提供新的见解,并可能为癌症治疗提出新的靶点。