The p48 subunit of the damaged-DNA binding protein DDB associates with the CBP/p300 family of histone acetyltransferase

Abhishek Datta , Srilata Bagchi , Alo Nag , Pavel Shiyanov , Guy R Adami , Taewon Yoon , Pradip Raychaudhuri
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引用次数: 149

Abstract

DDB has been implicated in DNA repair as well as transcription. Mutations in DDB have been correlated with the repair-deficiency disease, xeroderma pigmentosum group E (XP-E). The XP-E cells exhibit deficiencies in global genomic repair, suggesting a role for DDB in that process. DDB also possesses a transcription stimulatory activity. We showed that DDB could function as a transcriptional partner of E2F1. But the mechanism by which DDB stimulates E2F-regulated transcription or carry out its DNA repair function is not understood. To investigate the mechanisms, we looked for nuclear proteins that interact with DDB. Here we show that DDB associates with the CBP/p300 family of proteins, in vivo and in vitro. We suggest that DDB participates in global genomic repair by recruiting CBP/p300 to the damaged-chromatin. It is possible that the histone acetyltransferase activities of the CBP/p300 proteins induce chromatin remodeling at the damaged-sites to allow recruitment of the repair complexes. The observation offers insights into both transcription and repair functions of DDB.

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受损dna结合蛋白DDB的p48亚基与组蛋白乙酰转移酶的CBP/p300家族相关
DDB与DNA修复和转录有关。DDB突变与修复缺乏性疾病,色素性干皮病E组(XP-E)相关。XP-E细胞在全球基因组修复中表现出缺陷,表明DDB在这一过程中起作用。DDB还具有转录刺激活性。我们发现DDB可以作为E2F1的转录伙伴发挥作用。但DDB刺激e2f调控转录或执行其DNA修复功能的机制尚不清楚。为了研究其机制,我们寻找与DDB相互作用的核蛋白。本研究表明,DDB在体内和体外均与CBP/p300蛋白家族相关。我们认为DDB通过向受损染色质募集CBP/p300参与全球基因组修复。CBP/p300蛋白的组蛋白乙酰转移酶活性可能诱导受损部位的染色质重塑,从而允许修复复合物的招募。该观察结果为DDB的转录和修复功能提供了新的见解。
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