小柯机器人

美国国立卫生研究院的Wei Yang团队揭示XPC、TFIIH和XPA在DNA切除修复中的损伤识别。相关论文于2023年4月19日在线发表在《自然》杂志上。

研究人员报告了人类XPC识别DNA损伤和DNA损伤从XPC到7个亚单位的TFIIH核心复合体（Core7）和XPA的交接的结构。XPA结合在XPB和XPD之间，使DNA双链扭结，并使XPC和DNA病变相对于Core7移动近一个螺旋圈。因此，DNA损伤位于Core7之外，正如RNA聚合酶所发生的那样。XPB和XPD追踪含有损伤的链，但以相反的方向转移DNA，将含有损伤的链推拉到XPD中进行验证。

据了解，核苷酸切除修复可以消除由紫外线、顺铂类化合物和聚化加合物引起的DNA损伤。在全局基因组修复中，由XPC初步识别或在转录耦合修复中由停滞的RNA聚合酶识别后，受损的DNA被转移到Core7，进而由XPF和XPG核酸酶进行验证和双重切割。捕获酵母XPC同源物Rad4和TFIIH在转录起始或DNA修复中的损伤识别的结构已被分别报道。目前还不清楚两种不同的损伤识别途径如何汇合，以及Core7的XPB和XPD螺旋酶如何移动DNA损伤进行验证。

附：英文原文

Title: Lesion recognition by XPC, TFIIH and XPA in DNA excision repair

Author: Kim, Jinseok, Li, Chia-Lung, Chen, Xuemin, Cui, Yanxiang, Golebiowski, Filip M., Wang, Huaibin, Hanaoka, Fumio, Sugasawa, Kaoru, Yang, Wei

Issue&Volume: 2023-04-19

Abstract: Nucleotide excision repair removes DNA lesions caused by ultraviolet light, cisplatin-like compounds and bulky adducts1. After initial recognition by XPC in global genome repair or a stalled RNA polymerase in transcription-coupled repair, damaged DNA is transferred to the seven-subunit TFIIH core complex (Core7) for verification and dual incisions by the XPF and XPG nucleases2. Structures capturing lesion recognition by the yeast XPC homologue Rad4 and TFIIH in transcription initiation or DNA repair have been separately reported3,4,5,6,7. How two different lesion recognition pathways converge and how the XPB and XPD helicases of Core7 move the DNA lesion for verification are unclear. Here we report on structures revealing DNA lesion recognition by human XPC and DNA lesion hand-off from XPC to Core7 and XPA. XPA, which binds between XPB and XPD, kinks the DNA duplex and shifts XPC and the DNA lesion by nearly a helical turn relative to Core7. The DNA lesion is thus positioned outside of Core7, as would occur with RNA polymerase. XPB and XPD, which track the lesion-containing strand but translocate DNA in opposite directions, push and pull the lesion-containing strand into XPD for verification.

DOI: 10.1038/s41586-023-05959-z

Source: https://www.nature.com/articles/s41586-023-05959-z

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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