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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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Genre: Journal Article
Alternative Title : Curr. Biol.

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

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 Abstract: 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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Language(s): eng - English
 Dates: 2001-12-11
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 34941
ISI: 000172754700021
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Title: Current Biology
  Alternative Title : Curr. Biol.
Source Genre: Journal
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Publ. Info: -
Pages: - Volume / Issue: 11 (24) Sequence Number: - Start / End Page: 1934 - 1944 Identifier: ISSN: 0960-9822