The patchy human genome: DNA double-strand breaks in human cells can be repaired by the capture of other DNA fragments

The human genome is composed of very few genes (the DNA which encodes proteins), and the remaining 98% of all our DNA is made up of repetitive sequences or "junk" DNA with little or no known function. Our complexity, and the cause of many genetic diseases such as cancer, is brought about by the differential expression of that genetic material, in part due to shuffling and movement of chromosomes within the cell nucleus. A major threat to the integrity of the genome is the occurrence of a DNA double-strand break (DSB). These DSBs occur frequently in every cell, and if repaired improperly or left unattended can lead to genomic rearrangements and cell death. With the publication of the human genome sequence, we were able to establish two systems to investigate the possibility that DNA fragments can insert into breaks sites during DSB repair in human cells.;Our demonstration that DSB insertional repair takes place in human cells provides a mechanism for reshuffling genomic DNA, and acquiring new sequences. We propose that a selective advantage is conferred upon a cell able to insert DNA at a DSB, providing a complexity of gene content and interaction which could explain the origins and evolutionary role of the vast majority of the human genome.;We find that both foreign and human genomic DNA can insert into extrachromosomal and chromosomal DSBs. Genomic instability syndromes, like those which result from deficiencies in repair proteins, still permit this DSB insertional repair process, however the spectrum of source material provided can differ. The deregulation of replication origins, such as the amplification of sequences flanking viral integration sites, can lead to the spread and further gene amplification of DNA by this insertion mechanism.