Re therefore prone to different types of DSB mechanisms.Replication-induced DSBs During DNA replication, deletions can arise due to slippage of the synthesizing strand on the template strand. Chromosomal rearrangements that occur at specific hotspots, whether in cancer in somatic cells or during gametogenesis/initial developmental divisions as constitutional translocations, are called recurrent translocations that can be seen across many patients. Nonrecurrent translocations are those that occur at different locations from one patient to another but alter or inactivate a gene that causes a disease. Unlike the recurrent translocations that we have discussed in cancer above, the mechanisms that cause the strand exchange in nonrecurrent translocations appear to involve template switching during replicative DNA synthesis. These template switches can occur at small regions of DNA Quisinostat site sequence homology, such as 5 bp. This template switching has been called microhomology-mediated breakage-induced replication (MMBIR) or Fork Stalling and Template Switching (FoSTeS). For nonrecurrent translocation junctions that involve several long stretches of sequence from regions of the genome that are normally separated from one another, multiple template switching events has been proposed as a mechanism [38,39].Some DSBs arise at sites nearby direct or inverted DNA repeats. Such repeats may give rise to slipped DNA structures containing regions of single-stranded DNA, which may be targets for cleavage. The best example of this is the constitutional translocation t(11;22)(q23; q11), which contains an AT-rich palindrome of several hundred bases, with potential for cruciform formation.Combination of multiple DSB PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28388412 mechanisms within a rearrangement Given that two DSBs are required to generate a translocation, the two breaks are often not related to one another. In the bcl-2 and bcl-1 translocations, for example, the break at the IgH locus is a V(D)J-type break generated by the sequence-specific action of the RAG complex during V(D)J recombination. (One could consider this to be a failure in the completion of theBiological factors and neoplastic chromosomal translocationsThis review has not emphasized the neoplastic cellular proliferation advantage provided by these chromosomal rearrangements [40,41]. Rather, here we have focused on the factors that make some very focal (23 to 561 bp) DNA sequences particularly prone to repeated rearrangement events in a wide range of different patients, even though the translocations could have arisen within zones of 29 kb, as in the case of the bcl-2 gene or 100 kb, as in the bcl-1 translocation. Recurrent rearrangements found in particular cancers are oncogenic, and by nature provide a growth advantage.Page 6 of(page number not for citation purposes)BMC Genomics 2010, 11(suppl 1):Shttp://www.biomedcentral.com/1471-2164/11/S1/SSome such rearrangements result in the genesis of chimeric fusion transcripts between two genes, and such is the case for the t(1;19) translocation involving E2A and Pbx1 [42-47]. In these cases, the DSB could, in principle, occur across much of the length of a given intron within each gene so as to create the neoplastic fusion transcript. For the Pbx1 gene, the breaks occur diffusely in an intron in this way, and these DSBs are likely random and due to mechanisms such as free radical damage (i.e., ROS), ionizing radiation (IR), or topoisomerase failures. But the break at the E2A gene is focused to a 23 bp zo.