UV-damaged DNA-binding protein in the TFTC complex links DNA damage recognition to nucleosome acetylation
UV-damaged DNA-binding protein in the TFTC complex links DNA damage recognition to nucleosome acetylation
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DOI：
10.1093/emboj/20.12.3187
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发表时间：
2001-06-15
期刊：
影响因子：
11.4
通讯作者：
Tora, L
中科院分区：
文献类型：
--
作者：
Brand, M;Moggs, JG;Tora, L
RNA 聚合酶 II (Pol II) 启动蛋白质编码基因的转录被认为需要转录因子 TFIID，这是一种由 TATA 盒结合蛋白 (TBP) 和 TBP 相关因子 (TAF(II)s) 组成的复合物。在存在无 TBP 的 TAF(II) 复合物 (TFTC) 的情况下，可以在没有 TFIID 的情况下启动 Pol II 转录，含有 GCN5 乙酰转移酶的 TFTC 在核小体环境中乙酰化组蛋白 H3。我们已经鉴定出 TFTC (SAP130) 的一个 130 kDa 亚基，它与紫外线损伤 DNA 结合因子的大亚基具有同源性。 TFTC 优先结合紫外线照射的 DNA，紫外线损伤的 DNA 抑制 TFTC 介导的 Pol II 转录，并且 TFTC 与核苷酸切除修复蛋白 XP-A 并行招募到紫外线损伤的 DNA，TFTC 优先乙酰化组装在紫外线损伤的 DNA 上的核小体中的组蛋白 H3，与此一致，强组蛋白 H3 紫外线照射后，完整细胞中会发生乙酰化。这些结果表明，TFTC 可能通过染色质的共价修饰促进 DNA 修复机制接近染色质内的损伤。因此，我们的实验揭示了 DNA 损伤识别和染色质修饰之间的分子联系。
Initiation of transcription of protein-encoding genes by RNA polymerase II (Pol II) was thought to require transcription factor TFIID, a complex comprised of the TATA box-binding protein (TBP) and TBP-associated factors (TAF(II)s). In the presence of TBP-free TAF(II) complex (TFTC), initiation of Pol II transcription can occur in the absence of TFIID, TFTC containing the GCN5 acetyltransferase acetylates histone H3 in a nucleosomal context. We have identified a 130 kDa subunit of TFTC (SAP130) that shares homology with the large subunit of UV-damaged DNA-binding factor. TFTC preferentially binds UV-irradiated DNA, UV-damaged DNA inhibits TFTC-mediated Pol II transcription and TFTC is recruited in parallel with the nucleotide excision repair protein XP-A to UV-damaged DNA, TFTC preferentially acetylates histone H3 in nucleosomes assembled on UV-damaged DNA, In agreement with this, strong histone H3 acetylation occurs in intact cells after UV irradiation. These results suggest that the access of DNA repair machinery to lesions within chromatin may be facilitated by TFTC via covalent modification of chromatin, Thus, our experiments reveal a molecular link between DNA damage recognition and chromatin modification.