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Chipping away at gamma-H2AX foci
journal contribution
posted on 2023-06-08, 14:17 authored by Velibor Savic, Keri B Sanborn, Jordan S Orange, Craig H BassingThe mammalian histone H2AX protein functions as a dosage-dependent genomic caretaker and tumor suppressor. Phosphorylation of H2AX to form gamma-H2AX in chromatin around DNA double strand breaks (DSBs) is an early event following induction of these hazardous lesions. For a decade, mechanisms that regulate H2AX phosphorylation have been investigated mainly through two-dimensional immunofluorescence (IF). We recently used chromatin immunoprecipitation (ChIP) to measure gamma-H2AX densities along chromosomal DNA strands broken in G(1) phase mouse lymphocytes. Our experiments revealed that (1) gamma-H2AX densities in nucleosomes form at high levels near DSBs and at diminishing levels farther and farther away from DNA ends, and (2) ATM regulates H2AX phosphorylation through both MDC1-dependent and MDC1-independent means. Neither of these mechanisms were discovered by previous if studies due to the inherent limitations of light microscopy. Here, we compare data obtained from parallel gamma-H2AX ChIP and three-dimensional IF analyses and discuss the impact of our findings upon molecular mechanisms that regulate H2AX phosphorylation in chromatin around DNA breakage sites.
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Publication status
- Published
File Version
- Published version
Journal
Cell CycleISSN
1538-4101Publisher
Landes BioscienceExternal DOI
Issue
20Volume
8Page range
3285-3290Department affiliated with
- Clinical and Experimental Medicine Publications
Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2013-02-11First Open Access (FOA) Date
2013-02-11First Compliant Deposit (FCD) Date
2013-02-11Usage metrics
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