Mediate broke through with the PGA Tour Champions major victory nearly eight years after losing the 2008 U.S. Open at Torrey Pines to Tiger Woods on the first extra hole after an 18-hole playoff.
These values may be subject to alignment ambiguities caused by repeat-mediated breakpoints or microhomology generated by rearrangement mechanisms such as Fork Stalling Template Switching (FoSTeS) or microhomology mediated break induced replication (MMBIR) [ 33, 34].
Palindromes can be created by template switching of replication forks through microhomology (FoSTeS- Fork-Stalling and Template Switching) by Microhomology Mediated Break Induced Replication (MMBIR) [ 40– 43], or by foldback replication [ 13, 44].
DNA sequence analysis revealed that in six of nine deletions, both breakpoints occurred in the portions of Alu elements showing eight to 43 base pairs of perfect microhomology, suggesting replication error Microhomology-Mediated Break-Induced Replication (MMBIR)/Fork Stalling and Template Switching (FoSTeS) as a mechanism of their formation.
Mutations in xerC and dif confer modest sensitivity to EcoKI mediated breaks.
Previously reported candidates for CNV mechanisms include Non-Allelic Homologous Recombination (NAHR), Non-Homologous End Joining (NHEJ), Fork Stalling and Template Switching (FoSTeS) and Microhomology-Mediated Break-Induced Replication (MMBIR) [42].
Microhomology-mediated break-induced replication (MMBIR) have been proposed as one of the mechanism for microhomology-mediated rearrangements in plastids and mitochondria [ 44, 45].
Cytosine deamination to uracil results in base excision repair-mediated breaks initiated by uracil DNA glycosylase (Hitomi et al. 2007), suggesting that DNA damage other than directly formed DSBs can serve as recombination substrates potentially because of breaks made during other repair processes.
In addition, I-SceI mediated breaks at the active BES (upstream of the VSG and adjacent to the 70 bp repeats) trigger VSG switching, suggesting that these breaks mimic the natural triggers for switching (Boothroyd et al., 2009; Glover et al., 2013).
Mechanistically, the models currently used to explain CNV formation involve either non-allelic homologous recombination (NAHR) of (macro or micro) homologous tracks, or non-homologous (NH) repair mechanisms that are at play during replicative stress (e.g. Fork stalling and template switching (FoSTeS) or Microhomology-mediated break-induced replication (MMBIR) (Hastings et al., 2009)).
