Publication details

Local changes of higher-order chromatin structure during DSB-repair

Authors

FALK Martin LUKÁŠOVÁ Emilie GABRIELOVÁ Barbora ONDŘEJ Vladan KOZUBEK Stanislav

Year of publication 2008
Type Article in Periodical
Magazine / Source JOURNAL OF PHYSICS CONFERENCE SERIES
MU Faculty or unit

Faculty of Science

Citation
Field Biophysics
Keywords DOUBLE-STRAND BREAKS; HIGH-RESOLUTION CYTOMETRY; DNA-DAMAGE; CHROMOSOME DOMAINS; ACTIVE GENES; NUCLEI; SITES; PROTEINS; CELLS; TRANSCRIPTION
Description We show that double-strand breaks (DSBs) induced in DNA of human cells by gamma-radiation arise mainly in active, gene-rich, decondensed chromatin. We demonstrate that DSBs show limited movement in living cells, occasionally resulting in their permanent clustering, which poses a risk of incorrect DNA rejoining. In addition, some DSBs remain unrepaired for several days after irradiation, forming lesions repairable only with difficulty which are hazardous for genome stability. These late DSBs colocalize with heterochromatin markers (dimethylated histone H3 at lysine 9, HP1 and CENP-A proteins), despite the low density of the surrounding chromatin. This indicates that there is epigenetic silencing of loci close to unrepaired DSBs and/or stabilization of damaged decondensed chromatin loops during repair and post-repair reconstitution of chromatin structure.

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