Positional stability of single double-strand breaks in mammalian cells Journal Article
| Authors: | Soutoglou, E.; Dorn, J. F.; Sengupta, K.; Jasin, M.; Nussenzweig, A.; Ried, T.; Danuser, G.; Misteli, T. |
| Article Title: | Positional stability of single double-strand breaks in mammalian cells |
| Abstract: | Formation of cancerous translocations requires the illegitimate joining of chromosomes containing double-strand breaks (DSBs). It is unknown how broken chromosome ends find their translocation partners within the cell nucleus. Here, we have visualized and quantitatively analysed the dynamics of single DSBs in living mammalian cells. We demonstrate that broken ends are positionally stable and unable to roam the cell nucleus. Immobilization of broken chromosome ends requires the DNA-end binding protein Ku80, but is independent of DNA repair factors, H2AX, the MRN complex and the cohesion complex. DSBs preferentially undergo translocations with neighbouring chromosomes and loss of local positional constraint correlates with elevated genomic instability. These results support a contact-first model in which chromosome translocations predominantly form among spatially proximal DSBs. |
| Keywords: | controlled study; unclassified drug; dna binding protein; gene translocation; human cell; genetics; dna-binding proteins; cell cycle protein; cohesins; nonhistone protein; chromosome; mouse; animal; metabolism; mammalia; animals; cell cycle proteins; chromosomal proteins, non-histone; mice; dna damage; dna repair; nuclear protein; molecular dynamics; dna strand breakage; cell transformation, neoplastic; nuclear proteins; dna; double stranded dna; histone; cell transformation; genomic instability; quantitative analysis; dna breaks, double-stranded; chromosome translocation; double stranded dna break; translocation, genetic; cell nucleus; ku antigen; histone h2ax; histones; cell strain 3t3; nih 3t3 cells; chromosomes; macromolecule; macromolecular substances; molecular stability; antigens, nuclear; cell nucleus antigen; correlation function; protein ku80; h2ax protein, mouse |
| Journal Title: | Nature Cell Biology |
| Volume: | 9 |
| Issue: | 6 |
| ISSN: | 1465-7392 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2007-06-01 |
| Start Page: | 675 |
| End Page: | 682 |
| Language: | English |
| DOI: | 10.1038/ncb1591 |
| PUBMED: | 17486118 |
| PROVIDER: | scopus |
| PMCID: | PMC2442898 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 116" - "Export Date: 17 November 2011" - "CODEN: NCBIF" - "Source: Scopus" |
