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  C-elegans RAD-5/CLK-2 defines a new DNA damage checkpoint protein

Ahmed, S., Alpi, A., Hengartner, M. O., & Gartner, A. (2001). C-elegans RAD-5/CLK-2 defines a new DNA damage checkpoint protein. Current Biology, 11(24), 1934-1944.

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Datensatz-Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-70E8-2 Versions-Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-70E9-F
Genre: Zeitschriftenartikel
Alternativer Titel : Curr. Biol.

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 Urheber:
Ahmed, S., Autor
Alpi, A.1, Autor              
Hengartner, M. O., Autor
Gartner, A.1, Autor              
Affiliations:
1Former Research Groups, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565145              

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Schlagwörter: -
 Zusammenfassung: Background: In response to genotoxic stress, cells activate checkpoint pathways that lead to a transient cell cycle arrest that allows for DNA repair or to apoptosis, which triggers the demise of genetically damaged cells. Results: During positional cloning of the C. elegans rad-5 DNA damage checkpoint gene, we found, surprisingly, that rad-5(mn159) is allelic with clk- 2(qm37), a mutant previously implicated in regulation of biological rhythms and life span. However, clk-2(qm37) is the only C. elegans clock mutant that is defective for the DNA damage checkpoint. We show that rad-5/clk-2 acts in a pathway that partially overlaps with the conserved C. elegans mrt-2/S. cerevisiae RAD17/S. pombe rad1 (+) checkpoint pathway. In addition, rad-5/clk-2 also regulates the S phase replication checkpoint in C. elegans. Positional cloning reveals that the RAD-5/CLK-2 DNA damage checkpoint protein is homologous to S, cerevisiae Tel2p, an essential DNA binding protein that regulates telomere length in, yeast. However, the partial loss- of-function C. elegans rad-5(mn 159) and clk-2(qm37) checkpoint mutations have little effect on telomere length, and analysis of the partial loss-of-function of S. cerevisiae tel2-1 mutant failed to reveal typical DNA damage checkpoint defects. Conclusions: Using C. elegans genetics we define the novel DNA damage checkpoint protein RAD-5/CLK-2, which may play a role in oncogenesis. Given that Tel2p has been shown to bind to a variety of nucleic, acid structures in vitro, we speculate that the RAD-5/CLK-2 checkpoint protein may act at sites of DNA damage, either as a sensor of DNA damage or to aid in the repair of damaged DNA.

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Sprache(n): eng - Englisch
 Datum: 2001-12-11
 Publikationsstatus: Im Druck publiziert
 Seiten: -
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: eDoc: 34941
ISI: 000172754700021
 Art des Abschluß: -

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Titel: Current Biology
  Alternativer Titel : Curr. Biol.
Genre der Quelle: Zeitschrift
 Urheber:
Affiliations:
Ort, Verlag, Ausgabe: -
Seiten: - Band / Heft: 11 (24) Artikelnummer: - Start- / Endseite: 1934 - 1944 Identifikator: ISSN: 0960-9822