Damaged DNA-binding protein down-regulates epigenetic mark H3K56Ac through histone deacetylase 1 and 2.
Damaged DNA-binding protein down-regulates epigenetic mark H3K56Ac through histone deacetylase 1 and 2.
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DOI：
10.1016/j.mrfmmm.2015.01.005
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发表时间：
2015-06
影响因子：
2.3
通讯作者：
Wani, Altaf A.
中科院分区：
文献类型：
--
作者：
Zhu, Qianzheng;Battu, Aruna;Ray, Alo;Wani, Gulzar;Qian, Jiang;He, Jinshan;Wang, Qi-en;Wani, Altaf A.
关键词：
乙酰化组蛋白H3赖氨酸56 （H3K56Ac）是响应DNA损伤的可逆组蛋白翻译后修饰（PTMs）之一。我们之前描述了表观遗传标记H3K56Ac在紫外线辐射（UVR）诱导的DNA损伤下的双相减少和增加。在这里，我们报道了紫外线损伤dna结合蛋白（DDB）通过特异性组蛋白去乙酰化酶（HDACs）在H3K56Ac去乙酰化中的新功能。我们发现HDAC1/2的同时缺失会损害H3K56Ac的去乙酰化，而HDAC1或HDAC2的单独缺失对H3K56Ac没有影响。H3K56Ac去乙酰化不需要功能性核苷酸切除修复（NER）因子XPA和XPC，而是依赖上游因子DDB1和DDB2的功能。UVR增强了DDB2与HDAC1的关联，并且强制的DDB2表达导致HDAC1易位到UVR损伤的染色质上。HDAC1和HDAC2被招募到uvr诱导的DNA损伤点，用抗xpc免疫荧光显示。双HDAC1/2缺失减少XPC泛素化，但不影响DDB2对DNA损伤的招募。相比之下，γ - h2ax在uvr诱导的DNA损伤点的局部积累受到HDAC1和HDAC1/2双重消耗的影响。此外，uvr诱导的ATM激活在表达h3k56ac模拟H3K56Q的H12899细胞中降低。这些结果揭示了DDB在NER早期阶段H3K56Ac去乙酰化中的新作用，以及DDB介导的损伤识别与H3K56Ac去乙酰化之间存在活性功能串扰。
Acetylated histone H3 lysine 56 (H3K56Ac) is one of the reversible histone post-translational modifications (PTMs) responsive to DNA damage. We previously described a biphasic decrease and increase of epigenetic mark H3K56Ac in response to ultraviolet radiation (UVR)-induced DNA damage. Here, we report a new function of UV damaged DNA-binding protein (DDB) in deacetylation of H3K56Ac through specific histone deacetylases (HDACs). We show that simultaneous depletion of HDAC1/2 compromises the deacetylation of H3K56Ac, while depletion of HDAC1 or HDAC2 alone has no effect on H3K56Ac. The H3K56Ac deacetylation does not require functional nucleotide excision repair (NER) factors XPA and XPC, but depends on the function of upstream factors DDB1 and DDB2. UVR enhances the association of DDB2 with HDAC1 and, enforced DDB2 expression leads to translocation of HDAC1 to UVR-damaged chromatin. HDAC1 and HDAC2 are recruited to UVR-induced DNA damage spots, which are visualized by anti-XPC immunofluorescence. Dual HDAC1/2 depletion decreases XPC ubiquitination, but does not affect the recruitment of DDB2 to DNA damage. By contrast, the local accumulation of γH2AX at UVR-induced DNA damage spots was compromised upon HDAC1 as well as dual HDAC1/2 depletions. Additionally, UVR-induced ATM activation decreased in H12899 cells expressing H3K56Ac-mimicing H3K56Q. These results revealed a novel role of DDB in H3K56Ac deacetylation during early step of NER and the existence of active functional cross-talk between DDB-mediated damage recognition and H3K56Ac deacetylation.
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影响因子：
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通讯作者：
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ASF1A和ATM调节H3K56介导的细胞周期检查点响应紫外线照射。
影响因子：
14.9
作者：
Battu A;Ray A;Wani AA
通讯作者：
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