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Nucleic Acids Research 2004 32(20):6136-6143; doi:10.1093/nar/gkh952
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Published online 23 November 2004

Nucleic Acids Research, Vol. 32 No. 20 © Oxford University Press 2004; all rights reserved

Preferential accessibility to specific genomic loci for the repair of double-strand breaks in human cells

Hélène D'Anjou1, Catherine Chabot1,3 and Pierre Chartrand1,2,3,4,*

1 Molecular Biology Program and 2 Department of Pathology and Cellular Biology, 3 Montreal Cancer Institute, CHUM and 4 IRIC, Université de Montréal, Montréal, Québec, Canada

* To whom correspondence should be addressed. Tel: +1 514 343 6111, Ext. 3573; Fax: +1 514 343 7780; Email: pierre.chartrand{at}umontreal.ca

Received July 16, 2004; Revised October 8, 2004; Accepted November 1, 2004

The dynamic organization of the human genome in the nucleus is gaining recognition as a determining factor in its functional regulation. In order to be expressed, replicated or repaired, a genomic locus has to be present at the right place at the right time. In the present study, we have investigated the choice of a double-strand break (DSB) repair partner for a given genomic loci in an ATM-deficient human fibroblast cell line. We found that partner choice is restricted such that a given genomic locus preferentially uses certain sites in the genome to repair itself. These preferential sites can be in the vicinity of the damage site or megabases away or on other chromosomes entirely, while potential sites closer to the break along the length of the chromosome can be ignored. Moreover, there can be more than a 10-fold difference in usage between repair sites located only 10 kb apart. Interestingly, arms of a given chromosome are less accessible to one another than to other chromosomes. Altogether, these results indicate that the accessibility between genomic sites in the human genome during DSB repair is specific and conserved in a cell population.


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