Fatal connections: When DNA ends meet on the nuclear matrix

A damaged nucleus has long been regarded simply as a "bag of broken chromos omes," with the DNA free ends moving around and forming connections with ra ndomly encountered partners. Recent evidence shows this picture to be funda mentally wrong. Chromosomes occupy specific nuclear domains within which on ly limited movement is possible. In a human diploid nucleus, 6.6 x 10(9) ba se pairs (bp) of DNA are compartmentalized into chromosomes in a way that a llows stringent control of replication, differential gene expression, recom bination and repair. Most of the chromatin is further organized into looped domains by the dynamic binding of tethered bases to a network of intranucl ear proteins, the so-called nuclear scaffold or matrix. Thus, DNA movement is severely curtailed, which limits the number of sites where interchanges can occur. This intricate organizational arrangement may render the genome vulnerable to processes that interfere with DNA repair. Both lower and high er eukaryotic cells perform homologous recombination (HR) and illegitimate recombination (IR) as part of their survival strategies. The repair process es comprising IR must be understood in the context of DNA structural organi zation, which is fundamentally different in prokaryotic and eukaryotic geno mes. In this paper we first review important cellular processes including r ecombination, DNA repair, and apoptosis, and describe the central elements involved. Then we review the different DNA targets of recombination, and pr esent recent evidence implicating the nuclear matrix in processes which can induce either repair, translocation, deletion, or apoptosis. (C) 2001 Wile y-Liss, Inc.