Datta A, Bagchi S, Nag A, Shiyanov P, Adami G R, Yoon T, Raychaudhuri P
Department of Biochemistry and Molecular Biology (M/C 536), College of Medicine, University of Illinois at Chicago, 1819 W. Polk Street, Chicago, IL 60612, USA.
Mutat Res. 2001 Jul 12;486(2):89-97. doi: 10.1016/s0921-8777(01)00082-9.
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.
损伤特异性DNA结合蛋白(DDB)与DNA修复以及转录过程有关。DDB的突变与修复缺陷疾病——着色性干皮病E组(XP - E)相关。XP - E细胞在全基因组修复方面存在缺陷,这表明DDB在该过程中发挥作用。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。但DDB刺激E2F调控的转录或执行其DNA修复功能的机制尚不清楚。为了研究这些机制,我们寻找与DDB相互作用的核蛋白。在此我们表明,在体内和体外,DDB都与CBP/p300蛋白家族相关联。我们认为DDB通过将CBP/p300募集到受损染色质来参与全基因组修复。CBP/p300蛋白的组蛋白乙酰转移酶活性有可能在受损位点诱导染色质重塑,从而允许修复复合物的募集。这一观察结果为DDB的转录和修复功能提供了见解。