Links  |Sitemap  |  Contact  |  Home  |  中文   |  CAS
 HomeAbout UsResearchScientistsInt`l CooperationNews | Education & TrainingJoin UsPapersResources 
  New Papers
Multimedia
en20131028.jpg
The 5th International Conference on Rodent Biol...
Rodent adaptation and survival under global change
  Th...

Workshop on Phylogenetic comparative methods in...
The 31st IUBS GA and Conference on Biological ...
Special issue of Integrative Zoology: Biologica...
Exploring and integrating cellulolytic systems ...
      More>>
  Location: Home > New Papers
Ataxin-3 promotes genome integrity by stabilizing Chk1
[ Update Time: 2017-03-09 ]

The Chk1 protein is essential for genome integrity maintenance and cell survival in eukaryotic cells. After prolonged replication stress, Chk1 can be targeted for proteasomal degradation to terminate checkpoint signaling after DNA repair finishes. To ensure proper activation of DNA damage checkpoint and DNA repair signaling, a steady-state level of Chk1 needs to be retained under physiological conditions. Here, we report a dynamic signaling pathway that tightly regulates Chk1 stability. Under unperturbed conditions and upon DNA damage, ataxin-3 (ATX3) interacts with Chk1 and protects it from DDB1/CUL4A- and FBXO6/CUL1-mediated polyubiquitination and subsequent degradation, thereby promoting DNA repair and checkpoint signaling. Under prolonged replication stress, ATX3 dissociates from Chk1, concomitant with a stronger binding between Chk1 and its E3 ligase, which causes Chk1 proteasomal degradation. ATX3 deficiency results in pronounced reduction of Chk1 abundance, compromised DNA damage response, G2/M checkpoint defect and decreased cell survival after replication stress, which can all be rescued by ectopic expression of ATX3. Taken together, these findings reveal ATX3 to be a novel deubiquitinase of Chk1, providing a new mechanism of Chk1 stabilization in genome integrity maintenance.

https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkx095

 
Copyright ©1995-2017 INSTITUTE OF ZOOLOGY, CHINESE ACADEMY OF SCIENCES
Tel: +86-10-64807098, Fax: +86-10-64807099, Email: ioz@ioz.ac.cn
Address: 1 Beichen West Road, Chaoyang District, Beijing 100101, P.R.China
Internet Explorer 6.0+, best view with resolution 1024x768