RRC ID 3417
Author Parusel CT, Kritikou EA, Hengartner MO, Krek W, Gotta M.
Title URI-1 is required for DNA stability in C. elegans.
Journal Development
Abstract Unconventional prefoldin RPB5 interactor (URI), an evolutionary conserved member of the prefoldin family of molecular chaperones, plays a central role in the regulation of nutrient-sensitive, TOR (target-of-rapamycin)-dependent gene expression programs in yeast. Mammalian URI has been shown to associate with key components of the transcriptional machinery, including RPB5, a shared subunit of all three RNA polymerases, the ATPases TIP48 and TIP49, which are present in various chromatin remodeling complexes, and human PAF1 and parafibromin, which are components of a transcription elongation complex. Here, we provide the first functional characterization of a URI-1 homolog in a multicellular organism and show that the C. elegans gene uri-1 is essential for germ cell proliferation. URI-1-deficient cells exhibit cell cycle arrest and display DNA breaks as evidenced by TUNEL staining and the appearance of HUS-1::GFP foci formation. In addition, uri-1(lf) mutants and uri-1(RNAi) worms show a p53-dependent increase in germline apoptosis. Our findings indicate that URI-1 has an important function in the mitotic and meiotic cell cycles. Furthermore, they imply that URI-1 participates in a pathway(s) that is associated with the suppression of endogenous genotoxic DNA damage and highlight a role for URI-1 in the control of genome integrity.
Volume 133(4)
Pages 621-9
Published 2006-2
DOI 10.1242/dev.02235
PII 133/4/621
PMID 16436622
MeSH Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Proliferation DNA Damage* Genomic Instability* Germ Cells / physiology* Meiosis Mitosis Molecular Chaperones / genetics Molecular Chaperones / metabolism*
IF 5.763
Times Cited 34
C.elegans tm939