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| Human damage-specific DNA-binding protein p48 - Characterization of XPE mutations and regulation following UV irradiation |
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| Author(s): Nichols AF, Itoh T, Graham JA, Liu W, Yamaizumi M, Linn S |
| Source: JOURNAL OF BIOLOGICAL CHEMISTRY Volume: 275 Issue: 28 Pages: 21422-21428 Published: JUL 14 2000 |
| Times Cited: 75 References: 34 |
| Abstract: Damage-specific DNA binding (DDB) activity purifies from HeLa cells as a heterodimer (p127 and p48) and is absent from cells of a subset (Ddb(-)) of xeroderma pigmentosum Group E (XPE) patients. Each subunit was overexpressed in insect cells and purified. Both must be present for the damaged DNA band shift characteristic of the HeLa heterodimer. However, overexpressed p48 peptides containing the mutations found in three Ddb(-) XPE strains are inactive, and wild type p48 restores DDB activity to extracts from a fourth XPE Ddb(-) strain, GM01389, in which compound heterozygous mutations in DDB2 (p48) lead to a L350P change from one allele and a Asn-349 deletion from the other. Although these results indicate that these mutations are each responsible for the loss of DDB activity, they do not affect nuclear localization of p48. In normal fibroblasts, a 4-fold increase in p48 mRNA amount was observed 38 h after UV irradiation, preceding a similar elevation in p48 protein and DDB activity at 48 h, implying that p48 limits DDB activity in vivo. Because DNA repair is virtually complete before 48 h, a role for DDB other than DNA repair is suggested. |
| Document Type: Article |
| Language: English |
| Reprint Address: Linn, S (reprint author), Univ Calif Berkeley, Div Biochem & Mol Biol, 401 Barker Hall, Berkeley, CA 94720 USA |
Addresses:
1. Univ Calif Berkeley, Div Biochem & Mol Biol, Berkeley, CA 94720 USA
2. Kumamoto Univ, Sch Med, Inst Mol Embryol & Genet, Dept Cell Genet, Kumamoto 860, Japan |
| Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: 335EM |
| ISSN: 0021-9258 |
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