Sequential and ordered assembly of a large DNA repair complex on undamaged chromatin.
Sequential and ordered assembly of a large DNA repair complex on undamaged chromatin.
复制标题
DOI：
10.1083/jcb.201403096
复制
发表时间：
2014-09-01
期刊：
影响因子：
--
通讯作者：
Coin F
中科院分区：
文献类型：
--
作者：
Ziani S;Nagy Z;Alekseev S;Soutoglou E;Egly JM;Coin F
即使在没有 DNA 损伤的情况下，核苷酸切除修复预切割复合物也会通过顺序有序添加其各个亚基而在染色质上组装。在核苷酸切除修复 (NER) 中，XPC-hHR23b 的损伤识别被描述为形成切前复合物 (PInC) 的关键步骤，该复合物进一步由 TFIIH、XPA、RPA、XPG 和 ERCC1-XPF 组成。为了获得对 PInC 组装的新分子见解，我们使用乳糖操纵子/阻遏物报告系统独立于 DNA 损伤分析了其形成。我们观察到 PInC 在将单个 NER 因子固定在未受损的染色质上时进行连续有序的自组装，并模仿在真正的 NER 底物上的功能。我们还发现，参与毛发硫营养不良 A 组疾病 (TTD-A) 的 TFIIH 亚基 TTDA 的募集是完成 PInC 的关键。 TTDA 通过其前 15 个氨基酸招募 XPA，而这些氨基酸在一些 TTD-A 患者中已被耗尽。更一般地说，这些结果表明，形成大型核复合物的蛋白质可以在缺乏天然 DNA 靶标的情况下在染色质上顺序募集，并且在募集过程中没有互惠性。
The nucleotide excision repair preincision complex assembles on chromatin even in the absence of DNA damage through the sequential and ordered addition of its individual subunits. In nucleotide excision repair (NER), damage recognition by XPC-hHR23b is described as a critical step in the formation of the preincision complex (PInC) further composed of TFIIH, XPA, RPA, XPG, and ERCC1-XPF. To obtain new molecular insights into the assembly of the PInC, we analyzed its formation independently of DNA damage by using the lactose operator/repressor reporter system. We observed a sequential and ordered self-assembly of the PInC operating upon immobilization of individual NER factors on undamaged chromatin and mimicking that functioning on a bona fide NER substrate. We also revealed that the recruitment of the TFIIH subunit TTDA, involved in trichothiodystrophy group A disorder (TTD-A), was key in the completion of the PInC. TTDA recruits XPA through its first 15 amino acids, depleted in some TTD-A patients. More generally, these results show that proteins forming large nuclear complexes can be recruited sequentially on chromatin in the absence of their natural DNA target and with no reciprocity in their recruitment.
登录
查看更多内容
影响因子：
16
作者：
Fong, Yick W.;Cattoglio, Claudia;Tjian, Robert
通讯作者：
Tjian, Robert
影响因子：
16
作者：
Tang, JY;Hwang, BJ;Chu, G
通讯作者：
Chu, G
影响因子：
56.9
作者：
Kaiser, Trish E.;Intine, Robert V.;Dundr, Miroslav
通讯作者：
Dundr, Miroslav
影响因子：
8
作者：
Lemaitre, C.;Fischer, B.;Soutoglou, E.
通讯作者：
Soutoglou, E.
VP16酸性活化域诱导的大规模染色质展开和重塑。
影响因子：
7.8
作者：
Tumbar, T;Sudlow, G;Belmont, A S
通讯作者：
Belmont, A S