Document Detail


Deletion of DDB1 in mouse brain and lens leads to p53-dependent elimination of proliferating cells.
MedLine Citation:
PMID:  17129780     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
DDB1, a component of the Cul4 ubiquitin ligase complex, promotes protein ubiquitination in diverse cellular functions, including nuclear excision repair, regulation of the cell cycle, and DNA replication. To investigate its physiological significance, we generated mice with null and floxed alleles of the DDB1 gene. Here we report that null mutation of DDB1 caused early embryonic lethality, while conditional inactivation of the gene in brain and lens led to neuronal and lens degeneration, brain hemorrhages, and neonatal death. These defects stemmed from a selective elimination of nearly all proliferating neuronal progenitor cells and lens epithelial cells by apoptosis. The cell death was preceded by aberrant accumulation of cell cycle regulators and increased genomic instability and could be partially rescued by removal of the tumor suppressor protein p53. Our results indicate that DDB1 plays an essential role in maintaining viability and genomic integrity of dividing cells.
Authors:
Yong Cang; Jianxuan Zhang; Sally A Nicholas; Jayson Bastien; Baojie Li; Pengbo Zhou; Stephen P Goff
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell     Volume:  127     ISSN:  0092-8674     ISO Abbreviation:  Cell     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-11-28     Completed Date:  2007-01-09     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0413066     Medline TA:  Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  929-40     Citation Subset:  IM    
Affiliation:
Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
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MeSH Terms
Descriptor/Qualifier:
Alleles
Animals
Animals, Newborn
Apoptosis
Brain / abnormalities,  cytology*,  embryology,  pathology
Cell Cycle Proteins / metabolism
Cell Proliferation
Cell Survival
DNA Damage
DNA-Binding Proteins / deficiency*,  metabolism
Embryo, Mammalian / cytology
Embryonic Development
Fibroblasts / cytology
Gene Deletion*
Gene Targeting
Hemorrhage / pathology
Lens, Crystalline / abnormalities,  cytology*,  pathology
Mice
Mitosis
Neurons / cytology
Stem Cells / cytology
Tumor Suppressor Protein p53 / deficiency,  metabolism*
Grant Support
ID/Acronym/Agency:
CA 23767/CA/NCI NIH HHS; CA098210/CA/NCI NIH HHS; CA118085/CA/NCI NIH HHS; R37 CA 30488/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Cell Cycle Proteins; 0/DNA-Binding Proteins; 0/Ddb1 protein, mouse; 0/Ris2 protein, mouse; 0/Tumor Suppressor Protein p53

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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