Human ISWI complexes are targeted by SMARCA5 ATPase and SLIDE domains to help resolve lesion-stalled transcription
Human ISWI complexes are targeted by SMARCA5 ATPase and SLIDE domains to help resolve lesion-stalled transcription
复制标题
DOI：
10.1093/nar/gku565
复制
发表时间：
2014-01-01
影响因子：
14.9
通讯作者：
Lans, Hannes
中科院分区：
文献类型：
--
作者：
Aydin, Ozge Z.;Marteijn, Jurgen A.;Lans, Hannes
脱氧核糖核酸(DNA)的染色质致密是检测和去除DNA损伤的主要挑战。阻止转录的螺旋扭曲DNA损伤可以通过转录偶联核苷酸切除修复来特异性修复，该修复是由CSB蛋白与病变停滞的RNA聚合酶II结合启动的。利用活细胞成像，我们确定了两个不同的哺乳动物ISWI依赖的三磷酸腺苷(ATP)染色质重塑复合体在解决病变停滞转录中的新功能。人ISWI异构体SMARCA5/Snf2及其结合伙伴ACF1和WSTF被迅速招募到UV-C诱导的DNA损伤中，以特异性地促进CSB结合并促进转录恢复。针对UV-C损伤的SMARCA5依赖于转录和组蛋白修饰，需要具有功能的SWI2/SNF2-ATPase和Slide结构域。在最初募集到紫外线损伤后，SMARCA5重新定位于远离DNA损伤中心，需要它的手部结构域。我们的研究支持这样一个模型，即SMARCA5靶向DNA损伤停滞的转录位点是由依赖于ATP水解的扫描和校对机制控制的，强调了SWI2/SNF2染色质重构体是如何识别和结合包含受损DNA的核小体的。
Chromatin compaction of deoxyribonucleic acid (DNA) presents a major challenge to the detection and removal of DNA damage. Helix-distorting DNA lesions that block transcription are specifically repaired by transcription-coupled nucleotide excision repair, which is initiated by binding of the CSB protein to lesion-stalled RNA polymerase II. Using live cell imaging, we identify a novel function for two distinct mammalian ISWI adenosine triphosphate (ATP)-dependent chromatin remodeling complexes in resolving lesion-stalled transcription. Human ISWI isoform SMARCA5/SNF2H and its binding partners ACF1 and WSTF are rapidly recruited to UV-C induced DNA damage to specifically facilitate CSB binding and to promote transcription recovery. SMARCA5 targeting to UV-C damage depends on transcription and histone modifications and requires functional SWI2/SNF2-ATPase and SLIDE domains. After initial recruitment to UV damage, SMARCA5 re-localizes away from the center of DNA damage, requiring its HAND domain. Our studies support a model in which SMARCA5 targeting to DNA damage-stalled transcription sites is controlled by an ATP-hydrolysis-dependent scanning and proofreading mechanism, highlighting how SWI2/SNF2 chromatin remodelers identify and bind nucleosomes containing damaged DNA.