p48 Activates a UV-Damaged-DNA Binding Factor and Is Defective in Xeroderma Pigmentosum Group E Cells That Lack Binding Activity

Hwang, Byung Joon; Toering, Stephanie; Francke, Uta; Chu, Gilbert

doi:10.1128/mcb.18.7.4391

Cited by 147 publications

(164 citation statements)

References 47 publications

(53 reference statements)

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“…UV-DDB2 has emerged to be a critical factor for UV lesion detection and repair especially in the context of chromatin (26,27). To study the recruitment of DDB2 to UVdamaged chromatin, we analyzed the binding of DDB2 to chromatin from differences of resistance in loosely or tightly bound proteins to extraction in different concentrations of detergent and salt.…”

Section: Brg1 Depletion Affects Uv-induced Chromatin Remodeling But Hmentioning

confidence: 99%

Modulation of Nucleotide Excision Repair by Mammalian SWI/SNF Chromatin-remodeling Complex

Zhao

Wang

Ray

et al. 2009

Journal of Biological Chemistry

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Accessibility within chromatin is an important factor in the prompt removal of UV-induced DNA damage by nucleotide excision repair (NER). Chromatin remodeling by the SWI/SNF complex has been shown to play an important modulating role in NER in vitro and yeast in vivo. Nevertheless, the molecular basis of cross-talk between SWI/SNF and NER in mammalian cells is not fully understood. Here, we show that knockdown of Brg1, the ATPase subunit of SWI/SNF, negatively affects the elimination of cyclobutane pyrimidine dimers (CPD), but not of pyrimidine (6, 4)pyrimidone photoproducts (6-4PP) following UV irradiation of mammalian cells. Brg1-deficient cells exhibit a lower chromatin relaxation as well as impaired recruitment of downstream NER factors, XPG and PCNA, to UV lesions. However, the assembly of upstream NER factors, DDB2 and XPC, at the damage site was unaffected by Brg1 knockdown. Interestingly, Brg1 interacts with XPC within chromatin and is recruited to UV-damaged sites in a DDB2-and XPC-dependent manner. Also, postirradiation decrease of XPC levels occurred more rapidly in Brg1-deficient than normal cells. Conversely, XPC transcription remained unaltered upon Brg1 knockdown indicating that Brg1 affects the stability of XPC protein following irradiation. Thus, Brg1 facilitates different stages of NER by initially modulating UV-induced chromatin relaxation and stabilizing XPC at the damage sites, and subsequently stimulating the recruitment of XPG and PCNA to successfully culminate the repair.

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Section: Brg1 Depletion Affects Uv-induced Chromatin Remodeling But Hmentioning

confidence: 99%

Modulation of Nucleotide Excision Repair by Mammalian SWI/SNF Chromatin-remodeling Complex

Zhao

Wang

Ray

et al. 2009

Journal of Biological Chemistry

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“…Although this has been clearly demonstrated for Chinese hamster ovary cells (Hwang et al, 1998) and a few mouse fibroblast cell lines (Ishizaki et al, 1994;Tan and Chu, 2002), these data have frequently been inappropriately extrapolated to all 'rodent' cells. In particular, there is some evidence that this is not the case in certain mouse cells: for example, we have reported that the level of GGR, especially the repair of CPDs, was similar in primary mouse hepatocytes and human fibroblasts (Prost et al, 1998b).…”

Section: Introductionmentioning

confidence: 99%

E2F regulates DDB2: consequences for DNA repair in Rb-deficient cells

Prost

Caldwell

et al. 2006

Oncogene

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DDB2, a gene mutated in XPE patients, is involved in global genomic repair especially the repair of cyclobutane pyrimidine dimers (CPDs), and is regulated by p53 in human cells. We show that DDB2 is expressed in mouse tissues and demonstrate, using primary mouse epithelial cells, that mouse DDB2 is regulated by E2F transcription factors. Retinoblastoma (Rb), a tumor suppressor critical for the control of cell cycle progression, regulates E2F activity. Using Cre-Lox technology to delete Rb in primary mouse hepatocytes, we show that DDB2 gene expression increases, leading to elevated DDB2 protein levels. Furthermore, we show that endogenous E2F1 and E2F3 bind to DDB2 promoter and that treatment with E2F1-antisense or E2F1-small interfering RNA (siRNA) decreases DDB2 transcription, demonstrating that E2F1 is a transcriptional regulator for DDB2. This has consequences for global genomic repair: in Rb-null cells, where E2F activity is elevated, global DNA repair is increased and removal of CPDs is more efficient than in wild-type cells. Treatment with DDB2-siRNA decreases DDB2 expression and abolishes the repair phenotype of Rb-null cells. In summary, these results identify a new regulatory pathway for DDB2 by E2F, which does not require but is potentiated by p53, and demonstrate that DDB2 is involved in global repair in mouse epithelial cells.

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“…DDB2 is a subunit of the damaged-DNA recognition factor DDB, which binds to various forms of damaged-DNA, including UV-induced 6-4 photoproducts, cisplatin-modified DNA and bent DNA (Abramic et al, 1991;Hwang and Chu, 1993;Keeney et al, 1993;Hwang et al, 1998a;Fujiwara et al, 1999). Moreover, DDB2 has been shown to participate in global nucleotide excision repair (NER) (Hwang et al, 1998a;Tang et al, 2000;Wakasugi et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, DDB2 has been shown to participate in global nucleotide excision repair (NER) (Hwang et al, 1998a;Tang et al, 2000;Wakasugi et al, 2002). The proteins involved in the NER pathway are mutated in the eight different complementation groups of the repair-deficiency disease xeroderma pigmentosum (XP: A-G and V) (Friedberg et al, 1995;Sancar, 1996;Cleaver et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Tumor-prone phenotype of the DDB2-deficient mice

et al. 2004

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DDB2 is an essential subunit of the damaged-DNA recognition factor DDB, which is involved in global genomic repair in human cells. Moreover, DDB2 is mutated in the repair-deficiency disease xeroderma pigmentosum (Group E). Expression of DDB2 in human cells is induced by P53, BRCA1 and by ionizing radiation. The DDB2 protein associates with transcriptional activator and coactivator proteins. In addition, DDB2 in conjunction with DDB1 associates with cullin 4A and the Cop9/signalosome. We generated a mouse strain deficient for DDB2 (DDB2À/À). Consistent with the human disease (XP-E), the DDB2À/À mice were susceptible to UV-induced skin carcinogenesis. We observed a significant difference in the initial rate of cyclobutane pyrimidine dimer (CPD)-removal from the skin following UV irradiation. Also, the DDB2-deficient mice exhibited a significantly reduced life span compared to their wild-type littermates. Moreover, unlike other XP-deficient mice, the DDB2-deficient mice developed spontaneous malignant tumors at a high rate between the ages of 20 and 25 months. The observations suggest that, in addition to DNA repair, the other interactions of DDB2 are significant in its tumor suppression function.

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p48 Activates a UV-Damaged-DNA Binding Factor and Is Defective in Xeroderma Pigmentosum Group E Cells That Lack Binding Activity

Cited by 147 publications

References 47 publications

Modulation of Nucleotide Excision Repair by Mammalian SWI/SNF Chromatin-remodeling Complex

Modulation of Nucleotide Excision Repair by Mammalian SWI/SNF Chromatin-remodeling Complex

E2F regulates DDB2: consequences for DNA repair in Rb-deficient cells

Tumor-prone phenotype of the DDB2-deficient mice

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