URI-1 is required for DNA stability in C. elegans.
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.
Parusel
Christine T
CT
Eidgenoessische Technische Hochschule Zuerich, Institute of Cell Biology, CH-8093 Zuerich, Switzerland.
Kritikou
Ekaterini A
EA
Hengartner
Michael O
MO
Krek
Wilhelm
W
Gotta
Monica
M
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D004249:DNA Damage; D042822:Genomic Instability; D005854:Germ Cells / Q000502:physiology*; D008540:Meiosis; D008938:Mitosis; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D018832:Molecular Chaperones