| Complementary functions of ATM and H2AX in development and suppression of genomic instability. | |
| | |
MedLine Citation:
|
PMID: 18599436 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Upon DNA damage, histone H2AX is phosphorylated by ataxia-telangiectasia mutated (ATM) and other phosphoinositide 3-kinase-related protein kinases. To elucidate further the potential overlapping and unique functions of ATM and H2AX, we asked whether they have synergistic functions in the development and maintenance of genomic stability by inactivating both genes in mouse germ line. Combined ATM/H2AX deficiency caused embryonic lethality and dramatic cellular genomic instability. Mechanistically, severe genomic instability in the double-deficient cells is associated with a requirement for H2AX to repair oxidative DNA damage resulting from ATM deficiency. We discuss these findings in the context of synergies between ATM and other repair factors. |
| | |
Authors:
|
Shan Zha; JoAnn Sekiguchi; James W Brush; Craig H Bassing; Frederick W Alt |
Related Documents
:
|
16293626 - Dna damage promotes histone deacetylase 4 nuclear localization and repression of g2/m p... 18266976 - Expression of survivin protein in pterygium and relationship with oxidative dna damage. 7603496 - Cell cycle regulation of induced mutagenesis in yeast. 18790776 - Azd7762, a novel checkpoint kinase inhibitor, drives checkpoint abrogation and potentia... 9504426 - Identification of minimal orip of epstein-barr virus required for dna replication. 17389916 - Dna barcodes provide a quick preview of mitochondrial genome composition. |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2008-07-01 |
Journal Detail:
|
Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 105 ISSN: 1091-6490 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2008 Jul |
Date Detail:
|
Created Date: 2008-07-14 Completed Date: 2008-08-08 Revised Date: 2011-11-02 |
Medline Journal Info:
|
Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
|
Languages: eng Pagination: 9302-6 Citation Subset: IM |
Affiliation:
|
Howard Hughes Medical Institute, Children's Hospital, Immune Disease Institute, Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Cell Cycle Proteins / metabolism* Cell Proliferation DNA Damage DNA Repair DNA-Binding Proteins / metabolism* Embryo Loss / metabolism Embryo, Mammalian / abnormalities, metabolism Embryonic Stem Cells / metabolism Female Fibroblasts / metabolism, pathology Genomic Instability* Histones / metabolism* Mice Pregnancy Protein-Serine-Threonine Kinases / metabolism* Reactive Oxygen Species / metabolism Tumor Suppressor Proteins / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
|
5P01 CA109901-03/CA/NCI NIH HHS; 5P01 CA92625-06/CA/NCI NIH HHS; 5P01CA92625-06/CA/NCI NIH HHS; 5R01 CA125195-02/CA/NCI NIH HHS; R01 CA125195-02/CA/NCI NIH HHS; R01 CA125195-05/CA/NCI NIH HHS; //Howard Hughes Medical Institute |
| Chemical | |
Reg. No./Substance:
|
0/Cell Cycle Proteins; 0/DNA-Binding Proteins; 0/H2AX protein, mouse; 0/Histones; 0/Reactive Oxygen Species; 0/Tumor Suppressor Proteins; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/ataxia telangiectasia mutated protein |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Gene 1.7 of bacteriophage T7 confers sensitivity of phage growth to dideoxythymidine.
Next Document: Transcription factor MEF2C influences neural stem/progenitor cell differentiation and maturation in ...