Identification of genes that protect the C. elegans genome against mutations by genome-wide RNAi.

An RNA interference (RNAi)-based genome-wide screen was performed to detect genes that contribute to genome stability in somatic cells of Caenorhabditis elegans. We identified 61 such genes; these also affect spontaneous mutagenesis in the germ line. Their sequence suggests a role in DNA repair and/or replication, in chromatin remodeling, or in cell cycle control; there are also many novel genes that are highly conserved from yeast to human. Because known mutator genes are causally involved in many hereditary and sporadic human cancers, it is likely that some of these new mutators are equally relevant in cancer etiology.

[1]  R. Plasterk,et al.  Frequent germline mutations and somatic repeat instability in DNA mismatch-repair-deficient Caenorhabditis elegans. , 2002, Genetics.

[2]  T. Jenuwein,et al.  The many faces of histone lysine methylation. , 2002, Current opinion in cell biology.

[3]  Michel C. Nussenzweig,et al.  Genomic Instability in Mice Lacking Histone H2AX , 2002, Science.

[4]  Angelika Amon,et al.  Separase, Polo Kinase, the Kinetochore Protein Slk19, and Spo12 Function in a Network that Controls Cdc14 Localization during Early Anaphase , 2002, Cell.

[5]  M. Vidal,et al.  Combined Functional Genomic Maps of the C. elegans DNA Damage Response , 2002, Science.

[6]  A. Sugimoto,et al.  [Systematic functional analysis of the C. elegans genome]. , 2001, Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme.

[7]  Z. Wang.  Translesion synthesis by the UmuC family of DNA polymerases. , 2001, Mutation research.

[8]  A. Bürkle.  Poly(APD-ribosyl)ation, a DNA damage-driven protein modification and regulator of genomic instability. , 2001, Cancer letters.

[9]  L. Loeb.  A Mutator Phenotype in Cancer 1 , 2001 .

[10]  P. Zipperlen,et al.  Effectiveness of specific RNA-mediated interference through ingested double-stranded RNA in Caenorhabditis elegans , 2000, Genome Biology.

[11]  K. Struhl,et al.  Gcn4 activator targets Gcn5 histone acetyltransferase to specific promoters independently of transcription. , 2000, Molecular cell.

[12]  P. Zipperlen,et al.  Functional genomic analysis of C. elegans chromosome I by systematic RNA interference , 2000, Nature.

[13]  V. Reinke,et al.  A global profile of germline gene expression in C. elegans. , 2000, Molecular cell.

[14]  J. Walter,et al.  Initiation of eukaryotic DNA replication: origin unwinding and sequential chromatin association of Cdc45, RPA, and DNA polymerase alpha. , 2000, Molecular cell.

[15]  H. Pospiech,et al.  Nucleotide excision repair of DNA with recombinant human proteins: definition of the minimal set of factors, active forms of TFIIH, and modulation by CAK. , 2000, Genes & development.

[16]  A. Fire,et al.  Specific interference by ingested dsRNA , 1998, Nature.

[17]  S. Kowalczykowski,et al.  Rad52 protein stimulates DNA strand exchange by Rad51 and replication protein A , 1998, Nature.

[18]  D. Reinberg,et al.  Histone Deacetylases and SAP18, a Novel Polypeptide, Are Components of a Human Sin3 Complex , 1997, Cell.

[19]  R. Kolodner,et al.  Biochemistry and genetics of eukaryotic mismatch repair. , 1996, Genes & development.

[20]  P. Modrich,et al.  Mismatch repair in replication fidelity, genetic recombination, and cancer biology. , 1996, Annual review of biochemistry.

[21]  Robin J. Leach,et al.  Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer , 1993, Cell.

[22]  N. Copeland,et al.  The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. , 1993, Cell.

[23]  L. Loeb,et al.  Mutator phenotype may be required for multistage carcinogenesis. , 1991, Cancer research.

[24]  B. Vogelstein,et al.  A genetic model for colorectal tumorigenesis , 1990, Cell.

[25]  D. Baillie,et al.  Mutagenesis in Caenorhabditis elegans: I. A rapid eukaryotic mutagen test system using the reciprocal translocation, eTI(III;V) , 1983 .

[26]  H. Horvitz,et al.  unc-93(e1500): A behavioral mutant of Caenorhabditis elegans that defines a gene with a wild-type null phenotype. , 1980, Genetics.