Abstract
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.
MeSH Terms
Animals
Animals, Genetically Modified
Caenorhabditis elegans/genetics
Caenorhabditis elegans Proteins/classification,genetics
Cell Cycle/genetics
Chromatin/genetics,metabolism
DNA Repair/genetics
DNA Replication/genetics
Genes, Helminth
Genome
Helminth Proteins/genetics
Membrane Proteins
Muscle Proteins/genetics
Mutation
RNA Interference
RNA, Helminth
Sequence Homology, Nucleic Acid
Chemicals
Caenorhabditis elegans Proteins
Chromatin
Helminth Proteins
Membrane Proteins
Muscle Proteins
RNA, Helminth
unc-93 protein, C elegans
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Pothof Joris
Hubrecht Laboratory, Center for Biomedical Genetics, 3584 CT, Utrecht, The Netherlands.
van Haaften Gijs
Thijssen Karen
Kamath Ravi S
Fraser Andrew G
Ahringer Julie
Plasterk Ronald H A
Tijsterman Marcel
References (24)
24 references, click to expand
-
Nucleotide excision repair of DNA with recombinant human proteins: definition of the minimal set of factors, active forms of TFIIH, and modulation by CAK.
Genes Dev. 2000 Feb 1;14(3):349-59
PMID: 10673506
-
Specific interference by ingested dsRNA.
Nature. 1998 Oct 29;395(6705):854
PMID: 9804418
-
A global profile of germline gene expression in C. elegans.
Mol Cell. 2000 Sep;6(3):605-16
PMID: 11030340
-
Functional genomic analysis of C. elegans chromosome I by systematic RNA interference.
Nature. 2000 Nov 16;408(6810):325-30
PMID: 11099033
-
Poly(APD-ribosyl)ation, a DNA damage-driven protein modification and regulator of genomic instability.
Cancer Lett. 2001 Feb 10;163(1):1-5
PMID: 11163101
-
Gcn4 activator targets Gcn5 histone acetyltransferase to specific promoters independently of transcription.
Mol Cell. 2000 Dec;6(6):1309-20
PMID: 11163205
-
Effectiveness of specific RNA-mediated interference through ingested double-stranded RNA in Caenorhabditis elegans.
Genome Biol. 2001;2(1):RESEARCH0002
PMID: 11178279
-
A mutator phenotype in cancer.
Cancer Res. 2001 Apr 15;61(8):3230-9
PMID: 11309271
-
Translesion synthesis by the UmuC family of DNA polymerases.
Mutat Res. 2001 Jul 12;486(2):59-70
PMID: 11425512
-
Combined functional genomic maps of the C. elegans DNA damage response.
Science. 2002 Jan 4;295(5552):127-31
PMID: 11778048
-
Separase, polo kinase, the kinetochore protein Slk19, and Spo12 function in a network that controls Cdc14 localization during early anaphase.
Cell. 2002 Jan 25;108(2):207-20
PMID: 11832211
-
Genomic instability in mice lacking histone H2AX.
Science. 2002 May 3;296(5569):922-7
PMID: 11934988
-
The many faces of histone lysine methylation.
Curr Opin Cell Biol. 2002 Jun;14(3):286-98
PMID: 12067650
-
Frequent germline mutations and somatic repeat instability in DNA mismatch-repair-deficient Caenorhabditis elegans.
Genetics. 2002 Jun;161(2):651-60
PMID: 12072462
-
unc-93(e1500): A behavioral mutant of Caenorhabditis elegans that defines a gene with a wild-type null phenotype.
Genetics. 1980 Sep;96(1):147-64
PMID: 6894129
-
A genetic model for colorectal tumorigenesis.
Cell. 1990 Jun 1;61(5):759-67
PMID: 2188735
-
Mutator phenotype may be required for multistage carcinogenesis.
Cancer Res. 1991 Jun 15;51(12):3075-9
PMID: 2039987
-
The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer.
Cell. 1993 Dec 3;75(5):1027-38
PMID: 8252616
-
Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer.
Cell. 1993 Dec 17;75(6):1215-25
PMID: 8261515
-
Biochemistry and genetics of eukaryotic mismatch repair.
Genes Dev. 1996 Jun 15;10(12):1433-42
PMID: 8666228
-
Mismatch repair in replication fidelity, genetic recombination, and cancer biology.
Annu Rev Biochem. 1996;65:101-33
PMID: 8811176
-
Histone deacetylases and SAP18, a novel polypeptide, are components of a human Sin3 complex.
Cell. 1997 May 2;89(3):357-64
PMID: 9150135
-
Rad52 protein stimulates DNA strand exchange by Rad51 and replication protein A.
Nature. 1998 Jan 22;391(6665):407-10
PMID: 9450760
-
Initiation of eukaryotic DNA replication: origin unwinding and sequential chromatin association of Cdc45, RPA, and DNA polymerase alpha.
Mol Cell. 2000 Apr;5(4):617-27
PMID: 10882098