“Several studies have predicted that some CNV and nonrecurring copy number changes (CNC) in cancer cell lines, which are induced by aphidicolin or occur in some cases of Duchenne muscular dystrophy, Smith-Magenis syndrome, and Pelizaeus-Merzbacher disease, originate from nonhomologous end joining, fork stalling and template switching, or microhomology/microsatellite-induced replication mechanisms”
“(A) Infection-induced host DNA (green) double strand-break (DSB) and integration of kDNA minicircle sequence (blue) mediated by microhomology end-joining.”
“The occurrence of minicircles linked to LINE sequences via AC-rich microhomology-mediated recombination may augment endogenous levels of recombination, thus explaining the active generation of mosaic sequences and minicircle hitchhiking along with their associated retroposon, as seen in germ-line cells of Chagas patients and their progeny.”
“(C) Schematic representation of microhomology-mediated end-joining kDNA minicircle integration into retrotransposon LINE-1.”
“Here we have plotted the difference between the observed and expected amount of microhomology for our deletion breakpoints, which reveals two notable features of our data: (i) there are more deletion breakpoints showing microhomology than expected by chance; (ii) conditional on the presence of microhomology, there is an enrichment of breakpoints with 2 − 9 bases of microhomology.”
“The deletions are parsed by sequence features into three groups: the top group shows no microhomology or inserted sequence, the second group shows at least 1 bp of inserted sequence, represented by a blue line, and the third groups shows at least 1 bp of microhomology at the breakpoints, represented by green lines.”
“We derived an expected distribution of microhomology length by simulating random breakpoints while conditioning on the base content of CNV breakpoint regions.”
“The middle green sequences are short insertions from chromosome 14; considering a template model for their insertion, the sequences in red shading (TAA) would be microhomology between the DNA ends that could anneal to act as a primer, and the blue shading would represent microhomology for annealing after DNA synthesis between the two DNA ends (see text).”
“Sequences are annotated as follows: del, deletion length from the DNA end; underline, microhomology; +, length of long insertion.”
“Translocation breakpoint junctions have similar characteristics in wild-type cells and cells deficient in Xrcc4-ligase IV, including an unchanged bias toward microhomology, unlike what is observed for intrachromosomal DSB repair.”
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