Molecular cell, 2009-05, Vol.34 (3), p.298-310
2009
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Formation of Dynamic γ-H2AX Domains along Broken DNA Strands Is Distinctly Regulated by ATM and MDC1 and Dependent upon H2AX Densities in Chromatin
- Ist Teil von
- Molecular cell, 2009-05, Vol.34 (3), p.298-310
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2009
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- A hallmark of the cellular response to DNA double-strand breaks (DSBs) is histone H2AX phosphorylation in chromatin to generate γ-H2AX. Here, we demonstrate that γ-H2AX densities increase transiently along DNA strands as they are broken and repaired in G1 phase cells. The region across which γ-H2AX forms does not spread as DSBs persist; rather, γ-H2AX densities equilibrate at distinct levels within a fixed distance from DNA ends. Although both ATM and DNA-PKcs generate γ-H2AX, only ATM promotes γ-H2AX formation to maximal distance and maintains γ-H2AX densities. MDC1 is essential for γ-H2AX formation at high densities near DSBs, but not for generation of γ-H2AX over distal sequences. Reduced H2AX levels in chromatin impair the density, but not the distance, of γ-H2AX formed. Our data suggest that H2AX fuels a γ-H2AX self-reinforcing mechanism that retains MDC1 and activated ATM in chromatin near DSBs and promotes continued local phosphorylation of H2AX.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1097-2765eISSN: 1097-4164DOI: 10.1016/j.molcel.2009.04.012Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2744111
- Format
- –
- Schlagworte
- Animals, Ataxia Telangiectasia Mutated Proteins, B-Lymphocytes - cytology, B-Lymphocytes - physiology, Cell Cycle Proteins - genetics, Cell Cycle Proteins - metabolism, Chromatin - metabolism, DNA, DNA - metabolism, DNA Damage, DNA-Binding Proteins - genetics, DNA-Binding Proteins - metabolism, Endonucleases, G1 Phase - physiology, Genes, T-Cell Receptor alpha - genetics, Histones - genetics, Histones - metabolism, Intracellular Signaling Peptides and Proteins - genetics, Intracellular Signaling Peptides and Proteins - metabolism, Mice, Mice, Knockout, Nuclear Proteins - genetics, Nuclear Proteins - metabolism, Protein-Serine-Threonine Kinases - genetics, Protein-Serine-Threonine Kinases - metabolism, Recombination, Genetic, Thymus Gland - cytology, Tumor Suppressor Protein p53 - genetics, Tumor Suppressor Protein p53 - metabolism, Tumor Suppressor Proteins - genetics, Tumor Suppressor Proteins - metabolism