We have found and characterized an unusual extended area of DNA association with the nuclear matrix in the human dystrophin gene. This extended DNA loop anchorage region (LAR) has been mapped and characterized using a variety of biochemical and microscopy techniques. It spans approximately 200 kbp at chromosomal locations 950–1,150 Kb downstream to the beginning of the first exon of the dystrophin gene Dp427m and covers a part of the intron 43, exon 44, and most of intron 44. The extended LAR harbors the major recombination hot spot of the dystrophin gene and a replication origin. We propose a model where DNA topoisomerase II-mediated cleavage at the nuclear matrix may enhance recombination events within this extended LAR. J. Cell. Physiol. 209: 515–521, 2006. © 2006 Wiley-Liss, Inc.