Deutsch
 
Hilfe Datenschutzhinweis Impressum
  DetailsucheBrowse

Datensatz

 
 
DownloadE-Mail
  Caenorhabditis elegans HUS-1 is a DNA damage checkpoint protein required for genome stability and EGL-1-mediated apoptosis

Hofmann, E. R., Milstein, S., Boulton, S. J., Ye, M. J., Hofmann, J. J., Stergiou, L., et al. (2002). Caenorhabditis elegans HUS-1 is a DNA damage checkpoint protein required for genome stability and EGL-1-mediated apoptosis. Current Biology, 12(22), 1908-1918.

Item is

Basisdaten

einblenden: ausblenden:
Genre: Zeitschriftenartikel
Alternativer Titel : Curr. Biol.

Externe Referenzen

einblenden:

Urheber

einblenden:
ausblenden:
 Urheber:
Hofmann, E. R., Autor
Milstein, S., Autor
Boulton, S. J., Autor
Ye, M. J., Autor
Hofmann, J. J., Autor
Stergiou, L., Autor
Gartner, A.1, Autor           
Vidal, M., Autor
Hengartner, M. O., Autor
Affiliations:
1Former Research Groups, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565145              

Inhalt

einblenden:
ausblenden:
Schlagwörter: -
 Zusammenfassung: Background: The inability to efficiently repair DNA damage or remove cells with severely damaged genomes has been linked to several human cancers. Studies in yeasts and mammals have identified several genes that are required for proper activation of cell cycle checkpoints following various types of DNA damage. However, in metazoans, DNA damage can induce apoptosis as well. How DNA damage activates the apoptotic machinery is not fully understood. Results: We demonstrate here that the Caenorhabditis elegans gene hus-1 is required for DNA damage-induced cell cycle arrest and apoptosis. Following DNA damage, HUS-1 relocalizes and forms distinct foci that overlap with chromatin. Relocalization does not require the novel checkpoint protein RAD-5; rather, relocalization appears more frequently in rad-5 mutants, suggesting that RAD-5 plays a role in repair. HUS-1 is required for genome stability, as demonstrated by increased frequency of spontaneous mutations, chromosome nondisjunction, and telomere shortening. Finally, we show that DNA damage increases expression of the proapoptotic gene egl-1, a response that requires hus-1 and the p53 homolog cep-1. Conclusions: Our findings suggest that the RAD-5 checkpoint protein is not required for HUS-1 to relocalize following DNA damage. Furthermore, our studies reveal a new function of HUS-1 in the prevention of telomere shortening and mortalization of germ cells. DNA damage-induced germ cell death is abrogated in hus-1 mutants, in part, due to the inability of these mutants to activate egl-1 transcription in a cep- 1/p53dependent manner. Thus, HUS-1 is required for p53- dependent activation of a BH3 domain protein in C. elegans.

Details

einblenden:
ausblenden:
Sprache(n): eng - English
 Datum: 2002-11-19
 Publikationsstatus: Erschienen
 Seiten: -
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: eDoc: 41539
ISI: 000179486700017
 Art des Abschluß: -

Veranstaltung

einblenden:

Entscheidung

einblenden:

Projektinformation

einblenden:

Quelle 1

einblenden:
ausblenden:
Titel: Current Biology
  Alternativer Titel : Curr. Biol.
Genre der Quelle: Zeitschrift
 Urheber:
Affiliations:
Ort, Verlag, Ausgabe: -
Seiten: - Band / Heft: 12 (22) Artikelnummer: - Start- / Endseite: 1908 - 1918 Identifikator: ISSN: 0960-9822