Home LiteratureArticle Details
PMID: 1333609 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

RAD25 (SSL2), the yeast homolog of the human xeroderma pigmentosum group B DNA repair gene, is essential for viability.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 89 ·No. 23 ·1992-12-01 ·Pages 11416-20

Park E, Guzder SN, Koken MH, Jaspers-Dekker I, Weeda G, Hoeijmakers JH, Prakash S, Prakash L

Abstract

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(r) 95,356). The RAD25 (SSL2)- and XPBC-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 UV 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 Lys392 residue to arginine in the conserved Walker type A nucleotide-binding motif is lethal, suggesting an essential role of the putative RAD25 (SSL2) ATPase/DNA helicase activity in viability.

Related Genes
RAD25 RAD3 XPBC
MeSH Terms
Amino Acid Sequence Cloning, Molecular DNA Helicases/genetics DNA Repair Epistasis, Genetic Genes, Fungal Genes, Lethal Humans Molecular Sequence Data Saccharomyces cerevisiae/genetics Sequence Alignment Sequence Homology, Amino Acid Xeroderma Pigmentosum/genetics
Chemicals
DNA Helicases
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Park E
Department of Biophysics, University of Rochester School of Medicine, NY 14642.
Guzder S N
Koken M H
Jaspers-Dekker I
Weeda G
Hoeijmakers J H
Prakash S
Prakash L
References (37)
37 references, click to expand
  1. Molecular cloning of the human DNA excision repair gene ERCC-6.
    Mol Cell Biol. 1990 Nov;10(11):5806-13 PMID: 2172786
  2. Isolation and characterization of the RAD3 gene of Saccharomyces cerevisiae and inviability of rad3 deletion mutants.
    Proc Natl Acad Sci U S A. 1983 Sep;80(18):5680-4 PMID: 16593371
  3. SSL2, a suppressor of a stem-loop mutation in the HIS4 leader encodes the yeast homolog of human ERCC-3.
    Cell. 1992 Jun 12;69(6):1031-42 PMID: 1318786
  4. The purified yeast pre-mRNA splicing factor PRP2 is an RNA-dependent NTPase.
    EMBO J. 1992 Jun;11(6):2319-26 PMID: 1534753
  5. Yeast RAD14 and human xeroderma pigmentosum group A DNA-repair genes encode homologous proteins.
    Nature. 1992 Feb 6;355(6360):555-8 PMID: 1741034
  6. RAD10, an excision repair gene of Saccharomyces cerevisiae, is involved in the RAD1 pathway of mitotic recombination.
    Mol Cell Biol. 1990 Jun;10(6):2485-91 PMID: 2188090
  7. Transcription preferentially inhibits nucleotide excision repair of the template DNA strand in vitro.
    J Biol Chem. 1990 Dec 5;265(34):21330-6 PMID: 2250027
  8. The genetic defect in Cockayne syndrome is associated with a defect in repair of UV-induced DNA damage in transcriptionally active DNA.
    Proc Natl Acad Sci U S A. 1990 Jun;87(12):4707-11 PMID: 2352945
  9. Induction of the Escherichia coli lactose operon selectively increases repair of its transcribed DNA strand.
    Nature. 1989 Nov 2;342(6245):95-8 PMID: 2554145
  10. RAD3 protein of Saccharomyces cerevisiae is a DNA helicase.
    Proc Natl Acad Sci U S A. 1987 Dec;84(24):8951-5 PMID: 2827162
  11. The cloned human DNA excision repair gene ERCC-1 fails to correct xeroderma pigmentosum complementation groups A through I.
    Mutat Res. 1989 Mar;217(2):83-92 PMID: 2918869
  12. RAD1, an excision repair gene of Saccharomyces cerevisiae, is also involved in recombination.
    Mol Cell Biol. 1988 Sep;8(9):3619-26 PMID: 3065620
  13. Selective removal of transcription-blocking DNA damage from the transcribed strand of the mammalian DHFR gene.
    Cell. 1987 Oct 23;51(2):241-9 PMID: 3664636
  14. A DNA repair gene required for the incision of damaged DNA is essential for viability in Saccharomyces cerevisiae.
    Proc Natl Acad Sci U S A. 1983 Aug;80(15):4818-21 PMID: 6308653
  15. Novel Chinese hamster ultraviolet-sensitive mutants for excision repair form complementation groups 9 and 10.
    Cancer Res. 1991 Aug 1;51(15):3965-71 PMID: 1855213
  16. Isolation of two chloroethylnitrosourea-sensitive Chinese hamster cell lines.
    Cancer Res. 1991 Jan 1;51(1):195-8 PMID: 1899038
  17. A presumed DNA helicase encoded by ERCC-3 is involved in the human repair disorders xeroderma pigmentosum and Cockayne's syndrome.
    Cell. 1990 Aug 24;62(4):777-91 PMID: 2167179
  18. The rhp6+ gene of Schizosaccharomyces pombe: a structural and functional homolog of the RAD6 gene from the distantly related yeast Saccharomyces cerevisiae.
    EMBO J. 1990 May;9(5):1423-30 PMID: 2184030
  19. ERCC2: cDNA cloning and molecular characterization of a human nucleotide excision repair gene with high homology to yeast RAD3.
    EMBO J. 1990 May;9(5):1437-47 PMID: 2184031
  20. Analysis of a human DNA excision repair gene involved in group A xeroderma pigmentosum and containing a zinc-finger domain.
    Nature. 1990 Nov 1;348(6296):73-6 PMID: 2234061
  21. Isolation of the functional human excision repair gene ERCC5 by intercosmid recombination.
    Genomics. 1990 Dec;8(4):623-33 PMID: 2276736
  22. Molecular characterization of the human excision repair gene ERCC-1: cDNA cloning and amino acid homology with the yeast DNA repair gene RAD10.
    Cell. 1986 Mar 28;44(6):913-23 PMID: 2420469
  23. Two related superfamilies of putative helicases involved in replication, recombination, repair and expression of DNA and RNA genomes.
    Nucleic Acids Res. 1989 Jun 26;17(12):4713-30 PMID: 2546125
  24. Birth of the D-E-A-D box.
    Nature. 1989 Jan 12;337(6203):121-2 PMID: 2563148
  25. Mutation of lysine-48 to arginine in the yeast RAD3 protein abolishes its ATPase and DNA helicase activities but not the ability to bind ATP.
    EMBO J. 1988 Oct;7(10):3263-9 PMID: 2846277
  26. ATP-binding site of adenylate kinase: mechanistic implications of its homology with ras-encoded p21, F1-ATPase, and other nucleotide-binding proteins.
    Proc Natl Acad Sci U S A. 1986 Feb;83(4):907-11 PMID: 2869483
  27. The RAD3 gene of Saccharomyces cerevisiae encodes a DNA-dependent ATPase.
    Proc Natl Acad Sci U S A. 1987 Sep;84(17):6045-9 PMID: 2957691
  28. An eighth complementation group of rodent cells hypersensitive to ultraviolet radiation.
    Somat Cell Mol Genet. 1988 Nov;14(6):605-12 PMID: 3194799
  29. ATP-dependent unwinding of messenger RNA structure by eukaryotic initiation factors.
    J Biol Chem. 1985 Jun 25;260(12):7651-8 PMID: 3838990
  30. Genetic heterogeneity of xeroderma pigmentosum demonstrated by somatic cell hybridization.
    Nat New Biol. 1972 Jul 19;238(81):80-3 PMID: 4505415
  31. Distantly related sequences in the alpha- and beta-subunits of ATP synthase, myosin, kinases and other ATP-requiring enzymes and a common nucleotide binding fold.
    EMBO J. 1982;1(8):945-51 PMID: 6329717
  32. DNA sequencing with chain-terminating inhibitors.
    Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 PMID: 271968
  33. Workshop on DNA repair.
    Mutat Res. 1992 Jan;273(1):1-28 PMID: 1376432
  34. DNA.RNA helicase activity of RAD3 protein of Saccharomyces cerevisiae.
    Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9712-6 PMID: 1719538
  35. Renaturation of DNA catalysed by yeast DNA repair and recombination protein RAD10.
    Nature. 1992 Feb 20;355(6362):743-5 PMID: 1741062
  36. Xeroderma pigmentosum complementation group H falls into complementation group D.
    Mutat Res. 1991 Sep;255(2):201-8 PMID: 1922152
  37. Gene and transcription unit mapping by radiation effects.
    Annu Rev Genet. 1978;12:329-63 PMID: 371526
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.89.23.11416
Published
1992-12-01
Pages
11416-20
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC50561
Subset
IM
Grants
NCI NIH HHS · CA35035 · United States
NCI NIH HHS · CA41261 · United States
Databases
GENBANK
L01414
External Links
PubMed source DOI: 10.1073/pnas.89.23.11416 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2