Dynamics of DNA double-strand breaks revealed by clustering of damaged chromosome domains.
Interactions between ends from different DNA double-strand breaks (DSBs) can produce tumorigenic chromosome translocations. Two theories for the juxta-position of DSBs in translocations, the static "contact-first" and the dynamic "breakage-first" theory, differ fundamentally in their requirement for DSB mobility. To determine whether or not DSB-containing chromosome domains are mobile and can interact, we introduced linear tracks of DSBs in nuclei. We observed changes in track morphology within minutes after DSB induction, indicating movement of the domains. In a subpopulation of cells, the domains clustered. Juxtaposition of different DSB-containing chromosome domains through clustering, which was most extensive in G1 phase cells, suggests an adhesion process in which we implicate the Mre11 complex. Our results support the breakage-first theory to explain the origin of chromosomal translocations.
Aten
Jacob A
JA
Center for Microscopical Research, Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, Netherlands.
Stap
Jan
J
Krawczyk
Przemek M
PM
van Oven
Carel H
CH
Hoebe
Ron A
RA
Essers
Jeroen
J
Kanaar
Roland
R
D000512:Alpha Particles; D000818:Animals; D001260:Ataxia Telangiectasia / Q000235:genetics / Q000378:metabolism; D016466:CHO Cells; D002467:Cell Nucleus / Q000378:metabolism / Q000528:radiation effects; D019457:Chromosome Breakage; D002877:Chromosomes, Human / Q000378:metabolism*; D033481:Chromosomes, Mammalian / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000378:metabolism* / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D016193:G1 Phase; D016195:G2 Phase; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D000076228:MRE11 Homologue Protein; D010766:Phosphorylation; D051135:Rad51 Recombinase; D016196:S Phase; D014178:Translocation, Genetic
D004268:DNA-Binding Proteins; C468783:H2AX protein, human; D006657:Histones; C121766:MRE11 protein, human; D004247:DNA; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; D000076228:MRE11 Homologue Protein