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URI-1 is required for DNA stability in C. elegans.


Parusel, C T; Kritikou, E A; Hengartner, M O; Krek, W; Gotta, M (2006). URI-1 is required for DNA stability in C. elegans. Development, 113(4):621-629.

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.

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.

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Additional indexing

Item Type:Journal Article, refereed
Communities & Collections:07 Faculty of Science > Institute of Molecular Life Sciences
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:1 February 2006
Deposited On:11 Feb 2008 12:20
Last Modified:06 Dec 2017 13:06
Publisher:Company of Biologists
ISSN:0950-1991
Publisher DOI:https://doi.org/10.1242/dev.02235
PubMed ID:16436622

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