| Cdc5L interacts with ATR and is required for the S-phase cell-cycle checkpoint. | |
| | |
MedLine Citation:
|
PMID: 19633697 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Cell division cycle 5-like protein (Cdc5L) is a core component of the putative E3 ubiquitin ligase complex containing Prp19/Pso4, Plrg1 and Spf27. This complex has been shown to have a role in pre-messenger RNA splicing from yeast to humans; however, more recent studies have described a function for this complex in the cellular response to DNA damage. Here, we show that Cdc5L interacts physically with the cell-cycle checkpoint kinase ataxia-telangiectasia and Rad3-related (ATR). Depletion of Cdc5L by RNA-mediated interference methods results in a defective S-phase cell-cycle checkpoint and cellular sensitivity in response to replication-fork blocking agents. Furthermore, we show that Cdc5L is required for the activation of downstream effectors or mediators of ATR checkpoint function such as checkpoint kinase 1 (Chk1), cell cycle checkpoint protein Rad 17 (Rad17) and Fanconi anaemia complementation group D2 protein (FancD2). In addition, we have mapped the ATR-binding region in Cdc5L and show that a deletion mutant that is unable to interact with ATR is defective in the rescue of the checkpoint deficiency in Cdc5L-depleted cells. These findings show a new function for Cdc5L in the regulation of the ATR-mediated cell-cycle checkpoint in response to genotoxic agents. |
| | |
Authors:
|
Nianxiang Zhang; Ramandeep Kaur; Shamima Akhter; Randy J Legerski |
Related Documents
:
|
19597327 - The cyclin-dependent kinase inhibitors, cki-1 and cki-2, act in overlapping but distinc... 8380637 - Regulation of cell cycle progression and nuclear affinity of the retinoblastoma protein... 15201157 - Modulation of the cardiomyocyte cell cycle in genetically altered animals. 8986717 - A conserved degradation signal regulates rag-2 accumulation during cell division and li... 19597327 - The cyclin-dependent kinase inhibitors, cki-1 and cki-2, act in overlapping but distinc... 19780757 - Distinctive cell properties of b cells carrying the bcl2 translocation and their potent... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural Date: 2009-07-24 |
Journal Detail:
|
Title: EMBO reports Volume: 10 ISSN: 1469-3178 ISO Abbreviation: EMBO Rep. Publication Date: 2009 Sep |
Date Detail:
|
Created Date: 2009-09-01 Completed Date: 2009-11-10 Revised Date: 2010-09-02 |
Medline Journal Info:
|
Nlm Unique ID: 100963049 Medline TA: EMBO Rep Country: England |
Other Details:
|
Languages: eng Pagination: 1029-35 Citation Subset: IM |
Affiliation:
|
Department of Genetics, The University of Texas MD Anderson Cancer Center, University of Texas, 1515 Holcombe Boulevard, Houston, Texas 77030, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Cell Cycle Proteins
/
genetics,
metabolism* Cell Line DNA Damage Humans Mutation Protein Binding Protein-Serine-Threonine Kinases / genetics, metabolism* RNA, Small Interfering / genetics RNA-Binding Proteins / genetics, metabolism* S Phase* |
| Grant Support | |
ID/Acronym/Agency:
|
CA097175/CA/NCI NIH HHS; CA16672/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/CDC5L protein, human; 0/Cell Cycle Proteins; 0/RNA, Small Interfering; 0/RNA-Binding Proteins; EC 2.7.1.-/ATR protein, human; EC 2.7.11.1/Protein-Serine-Threonine Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: HAT-HDAC interplay modulates global histone H3K14 acetylation in gene-coding regions during stress.
Next Document: Observation of the density and size of cells in hippocampus and vascular lesion in thalamus of GFAP-...