RAD25 (SSL2), the yeast homolog of the human xeroderma pigmentosum group B DNA repair gene, is essential for viability
- Univ. of Rochester School of Medicine, NY (United States)
- Univ. of Rochester, NY (United States)
- Erasmus Univ., Rotterdam (Netherlands)
Xeroderma pigmentosum (XP) patients are extremely sensitive to ultraviolet (UV) light and suffer from a high incidence of skin cancers, due to a defect in nucleotide excision repair. The disease is genetically heterogeneous, and seven complementation groups, A-G, have been identified. Homologs of human excision repair genes ERCC1, XPDC/ERCC2, and XPAC have been identified in the yeast Saccharomyces cerevisiae. Since no homolog of human XPBC/ERCC3 existed among the known yeast genes, we cloned the yeast homolog by using XPBC cDNA as a hybridization probe. The yeast homolog, RAD25 (SSL2), encodes a protein of 843 amino acids (M[sub r] 95,356). The RAD25 (SSL2)- and XPCX-encoded proteins share 55% identical and 72% conserved amino acid residues, and the two proteins resemble one another in containing the conserved DNA helicase sequence motifs. A nonsense mutation at codon 799 that deletes the 45 C-terminal amino acid residues in RAD25 (SSL2) confers UV sensitivity. This mutation shows epistasis with genes in the excision repair group, whereas a synergistic increase in UN sensitivity occurs when it is combined with mutations in genes in other DNA repair pathways, indicating that RAD25 (SSL2) functions in excision repair but not in other repair pathways. We also show that RAD25 (SSL2) is an essential gene. A mutation of the Lys[sup 392] residue to arginine in the conserved Walker type A nucleotide-binding motif is lethal, suggesting an essential role of the putative RAD 25 (SSL2) ATPase/DNA helicase activity in viability. 40 refs., 3 figs., 1 tab.
- OSTI ID:
- 6199966
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 89:23; ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
DNA REPAIR
BIOLOGICAL PATHWAYS
HUMAN POPULATIONS
SKIN DISEASES
AMINO ACIDS
ARGININE
DNA
EXCISION REPAIR
GENES
MUTATIONS
PATIENTS
PROTEINS
SACCHAROMYCES CEREVISIAE
ULTRAVIOLET RADIATION
VIABILITY
XERODERMA PIGMENTOSUM
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CARBOXYLIC ACIDS
CONGENITAL DISEASES
DISEASES
ELECTROMAGNETIC RADIATION
EUMYCOTA
FUNGI
HEREDITARY DISEASES
MICROORGANISMS
NUCLEIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
PLANTS
POPULATIONS
RADIATIONS
REPAIR
SACCHAROMYCES
YEASTS
550200* - Biochemistry
550400 - Genetics