Here we review how these alternative HDR pathways are executed, specifically focusing on the determinants that dictate competition between them and their relevance to cancers that display complex genomic rearrangements or maintain their telomeres by homologydirected DNA synthesis.Doublestrand break repair is essential to all forms of life.The canonical and predominant pathways of DSB repair include gene conversion. Starting from ssDNA overhangs, numerous alternative forms of errorprone HDR pathways can be invoked.Emerging evidence indicates their central involvement in the genomic instability that is present in cancers and other congenital disorders. This review describes the basis for several different forms of noncanonical HDR and highlights the discovery and conservation of these DNA repair mechanisms across prokaryotic and eukaryotic organisms.Where possible, we attempt to delineate determinants of competition between these distinct DNA repair mechanisms.We begin with the twoended DSB repair pathways and compare the biochemical mechanisms and the molecular machinery used by these and the GC pathway. Finally, we focus on various forms of mutagenic oneended DSB repair pathways and review recent studies on alternative forms of telomere maintenance and genomic rearrangements that arise from varied themes of oneended break repair mechanisms.Extensive bidirectional resection reveals complementary ssDNA sequences that can then anneal.Singlestranded annealing use the same end resection machinery as the GC pathway.SSA or MMEJ operates in the absence of singlestranded tail invasion into a homologous template.If the sequences revealed after resection are direct repeats, SSA is favored over MMEJ.Repair by SDSA occurs when the invading strand, after undergoing limited DNA synthesis, is displaced from the D loop by a helicase and anneals back to a complementary strand.Mammalian proteins required for each pathway are shown; those proteins for which direct evidence is currently lacking are followed by a question mark.A twostaged DNA repair process was suggested to accomplish this reassembly.The subsequent annealing of the two complementary strands is similar to the SSA pathway.Most of the repair products were associated with the deletion of one or more repeat units.This observation was subsequently explained using an SSA mechanism that had already been proposed in a mammalian system showed that the DSB repair product of a plasmid with two copies of the same gene in direct orientation was associated with the annealing of the homologous sequences with concomitant deletion of one of the repeats and the intervening DNA.Unlike GC, the kinetics of SSA product formation were inversely related to the distance between the repeats. This end resection machinery is used by other HDR pathways as well.Rad is also required for SSA, <a href="http://www.targetmol.com/compound/Vitamin-K1"></a>
particularly in the context of annealing shorter regions of homology. It was demonstrated that, when two homologous segments are in direct orientation, SSA predominates over GC. However, in a rad deletion strain, there is a marked increase in SSA with a concomitant decrease in GC, exemplifying the competing nature of the two pathways. Unlike most other DNA repair pathways that were discovered in bacteria and yeast, the SSA mode of recombination was first identified in mammalian cells.It was observed that the efficiency of both intermolecular and intramolecular recombination of plasmids with sequence repeats was dependent on the degree of homology and could be stimulated fold to fold by appropriately cutting the DNA relative to the recombining sequences.