Chromatin mobility is increased at sites of DNA double-strand breaks.
DNA double-strand breaks (DSBs) can efficiently kill cancer cells, but they can also produce unwanted chromosome rearrangements when DNA ends from different DSBs are erroneously joined. Movement of DSB-containing chromatin domains might facilitate these DSB interactions and promote the formation of chromosome rearrangements. Therefore, we analyzed the mobility of chromatin domains containing DSBs, marked by the fluorescently tagged DSB marker 53BP1, in living mammalian cells and compared it with the mobility of undamaged chromatin on a time-scale relevant for DSB repair. We found that chromatin domains containing DSBs are substantially more mobile than intact chromatin, and are capable of roaming a more than twofold larger area of the cell nucleus. Moreover, this increased DSB mobility, but not the mobility of undamaged chromatin, can be reduced by agents that affect higher-order chromatin organization.
van Leeuwenhoek Centre for Advanced Microscopy-AMC, Department of Cell Biology & Histology, University of Amsterdam, Amsterdam, The Netherlands. p.krawczyk@amc.uva.nl
P M
PM
Krawczyk
T
T
Borovski
J
J
Stap
T
T
Cijsouw
R
R
ten Cate
J P
JP
Medema
R
R
Kanaar
N A P
NA
Franken
J A
JA
Aten
D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects; D002843:Chromatin / Q000187:drug effects / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects; D002869:Chromosome Aberrations / Q000187:drug effects / Q000528:radiation effects; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics*; D005047:Etoposide / Q000494:pharmacology; D005453:Fluorescence; D005720:Gamma Rays; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D009038:Motion; D010957:Plasmids; D013194:Staining and Labeling; D059008:Time-Lapse Imaging; D014162:Transfection; D000071857:Tumor Suppressor p53-Binding Protein 1
D002843:Chromatin; D047908:Intracellular Signaling Peptides and Proteins; C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1; D005047:Etoposide