A constitutive damage-specific DNA-binding protein is synthesized at higher levels in UV-irradiated primate cells.

Hirschfeld, Steven; Levine, Arthur S.; Ozato, Keiko; Protić, Miroslava

doi:10.1128/mcb.10.5.2041

Cited by 97 publications

(71 citation statements)

References 37 publications

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“…4A to 6) suggests a possible recruitment and therefore concentration of Gadd45 at sites where the nucleosomes have been weakened by either histone posttranslational modifications or DNA damage. While binding of sequence specific transcription factors is generally inhibited on UV-damaged templates (66,73), it is apparently increased for proteins recognizing altered DNA structure (8,25,39,45,63). For example, the high-mobility-group protein HMG1 has recently been shown to bind preferentially to UV-damaged DNA (45).…”

Section: Discussionmentioning

confidence: 99%

Gadd45, a p53-Responsive Stress Protein, Modifies DNA Accessibility on Damaged Chromatin

Georgel

Pourquier

Blake³

et al. 1999

Molecular and Cellular Biology

252

179

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This report demonstrates that Gadd45, a p53-responsive stress protein, can facilitate topoisomerase relaxing and cleavage activity in the presence of core histones. A correlation between reduced expression of Gadd45 and increased resistance to topoisomerase I and topoisomerase II inhibitors in a variety of human cell lines was also found. Gadd45 could potentially mediate this effect by destabilizing histone-DNA interactions since it was found to interact directly with the four core histones. To evaluate this possibility, we investigated the effect of Gadd45 on preassembled mononucleosomes. Our data indicate that Gadd45 directly associates with mononucleosomes that have been altered by histone acetylation or UV radiation. This interaction resulted in increased DNase I accessibility on hyperacetylated mononucleosomes and substantial reduction of T4 endonuclease V accessibility to cyclobutane pyrimidine dimers on UV-irradiated mononucleosomes but not on naked DNA. Both histone acetylation and UV radiation are thought to destabilize the nucleosomal structure. Hence, these results imply that Gadd45 can recognize an altered chromatin state and modulate DNA accessibility to cellular proteins.

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Section: Discussionmentioning

confidence: 99%

Gadd45, a p53-Responsive Stress Protein, Modifies DNA Accessibility on Damaged Chromatin

Georgel

Pourquier

Blake³

et al. 1999

Molecular and Cellular Biology

252

179

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“…25,26 Cell strains from a subset (Ddb-) of individuals carrying XP complementation group E (XPE) lack a damage-specific DNA binding protein p48 (DDB2) activity. [27][28][29] Because DDB2 was reported to recognize many types of DNA lesions [30][31][32][33][34][35] and is inducible by treatment with DNA damaging agents, 32,36,37 DDB2 was expected to play a role in damage recognition prior to NER. Several observations have challenged the role of DDB2 in NER.…”

Section: Introductionmentioning

confidence: 99%

BRCA1 Transcriptionally Regulates Damaged DNA Binding Protein (DDB2) In the DNA Repair Response Following UV-Irradiation

Takimoto¹,

MacLachlan²,

Dicker³

et al. 2002

Cancer Biology & Therapy

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© 2 0 0 2 L a n d e s B i o s c i e n c e . N o t f o r d i s t r i b u t i o n .[Cancer Biology & ABSTRACTThe p53 and BRCA1 tumor suppressors are involved in repair processes and may cooperate to transactivate certain genes, including p21WAF1/CIP1 and GADD45. We find that the Xeroderma Pigmentosum Complementation group E (XPE) mutated Damaged-DNA binding protein p48 (DDB2) is upregulated by BRCA1 in a p53-dependent manner following UVC, Adriamycin, or Cisplatin exposure. BRCA1 enhances p53 binding to the DDB2 promoter in vivo as well as p53-dependent transactivation of DDB2 promoterreporter constructs through a classical p53 DNA responsive element. Antisense abrogation of BRCA1 expression abrogates upregulation of DDB2 after UVC or cisplatin exposure. Using a host cell reactivation assay, DNA repair activity is more significantly restored by introduction of BRCA1 into wt as compared to DDB2-deficient cells. Furthermore disappearance of the photoproducts cyclobutane pyrimidine dimer (CPD) and 6-4 photoproduct (6-4PP) was delayed by antisense abrogation of BRCA1 expression in UV-exposed human cells. Thus the DNA repair function of BRCA1 may be attributed in part to p53-dependent transcriptional induction of DDB2. Loss of BRCA1-dependent DDB2 repair function may contribute to cancer susceptibility and cellular sensitivity to DNA damage.

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“…Human and monkey cells contain a binding activity which has high specificity for DNA damaged by UV but which also recognizes DNA damaged by cisplatin, nitrogen mustard, denaturation, and depurination (6,7,19,33). This UV-damaged-DNA binding (UV-DDB) activity appears to play a role in nucleotide excision repair: it is absent in a subset of XP group E cells, which like all XP cells are deficient in DNA repair (7,22,27), and it is expressed at higher levels in human tumor cell lines, which were selected for resistance to cisplatin and which display cross-resistance to UV radiation and enhanced DNA repair (6).…”

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confidence: 99%

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

Hwang

Toering²,

Francke

et al. 1998

Molecular and Cellular Biology

147

156

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A subset of xeroderma pigmentosum (XP) group E cells lack a factor that binds to DNA damaged by UV radiation. This factor can be purified to homogeneity as p125, a 125-kDa polypeptide. However, when cDNA encoding p125 is translated in vitro, only a small fraction binds to UV-damaged DNA, suggesting that a second factor is required for the activation of p125. We discovered that most hamster cell lines expressed inactive p125, which was activated in somatic cell hybrids containing human chromosome region 11p11.2-11cen. This region excluded p125 but included p48, which encodes a 48-kDa polypeptide known to copurify with p125 under some conditions. Expression of human p48 activated p125 binding in hamster cells and increased p125 binding in human cells. No such effects were observed from expression of p48 containing single amino acid substitutions from XP group E cells that lacked binding activity, demonstrating that the p48 gene is defective in those cells. Activation of p125 occurred by a "hit-and-run" mechanism, since the presence of p48 was not required for subsequent binding. Nevertheless, p48 was capable of forming a complex with p125 either bound to UVdamaged DNA or in free solution. It is notable that hamster cells fail to efficiently repair cyclobutane pyrimidine dimers in nontranscribed DNA and fail to express p48, which contains a WD motif with homology to proteins that reorganize chromatin. We propose that p48 plays a role in repairing lesions that would otherwise remain inaccessible in nontranscribed chromatin.

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A constitutive damage-specific DNA-binding protein is synthesized at higher levels in UV-irradiated primate cells.

Cited by 97 publications

References 37 publications

Gadd45, a p53-Responsive Stress Protein, Modifies DNA Accessibility on Damaged Chromatin

Gadd45, a p53-Responsive Stress Protein, Modifies DNA Accessibility on Damaged Chromatin

BRCA1 Transcriptionally Regulates Damaged DNA Binding Protein (DDB2) In the DNA Repair Response Following UV-Irradiation

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

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