Xeroderma Pigmentosum p48 Gene Enhances Global Genomic Repair and Suppresses UV-Induced Mutagenesis

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Xeroderma pigmentosum p48 gene enhances global genomic repair and suppresses UV-induced mutagenesis.

UV-damaged DNA-binding activity (UV-DDB) is deficient in some xeroderma pigmentosum group E individuals due to mutation of the p48 gene, but its role in DNA repair has been obscure. We found that UV-DDB is also deficient in cell lines and primary tissues from rodents. Transfection of p48 conferred UV-DDB to hamster cells, and enhanced removal of cyclobutane pyrimidine dimers (CPDs) from genomic...

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Expression of the p48 xeroderma pigmentosum gene is p53-dependent and is involved in global genomic repair.

In human cells, efficient global genomic repair of DNA damage induced by ultraviolet radiation requires the p53 tumor suppressor, but the mechanism has been unclear. The p48 gene is required for expression of an ultraviolet radiation-damaged DNA binding activity and is disrupted by mutations in the subset of xeroderma pigmentosum group E cells that lack this activity. Here, we show that p48 mRN...

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Melanocyte-stimulating hormone directly enhances UV-Induced DNA repair in keratinocytes by a xeroderma pigmentosum group A-dependent mechanism.

Melanocyte-stimulating hormone (MSH) reduces UV-induced DNA damage through the induction of pigmentation. In this study, we provide evidence that MSH also enhances DNA repair in skin keratinocytes by modulating the function of DNA repair molecules. Intracutaneous injection of MSH prevented UV-induced DNA damage in human and mouse skin independent of its effects on melanogenesis. In keratinocyte...

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p53 Binds and activates the xeroderma pigmentosum DDB2 gene in humans but not mice.

The DDB2 gene, which is mutated in xeroderma pigmentosum group E, enhances global genomic repair of cyclobutane pyrimidine dimers and suppresses UV-induced mutagenesis. Because DDB2 transcription increases after DNA damage in a p53-dependent manner, we searched for and found a region in the human DDB2 gene that binds and responds transcriptionally to p53. The corresponding region in the mouse D...

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Xeroderma Pigmentosum Group A Suppresses Mutagenesis Caused by Clustered Oxidative DNA Adducts in the Human Genome

Clustered DNA damage is defined as multiple sites of DNA damage within one or two helical turns of the duplex DNA. This complex damage is often formed by exposure of the genome to ionizing radiation and is difficult to repair. The mutagenic potential and repair mechanisms of clustered DNA damage in human cells remain to be elucidated. In this study, we investigated the involvement of nucleotide...

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ژورنال

عنوان ژورنال: Molecular Cell

سال: 2000

ISSN: 1097-2765

DOI: 10.1016/s1097-2765(00)80252-x