Locus-specific control of DNA resection and suppression of subtelomeric VSG recombination by HAT3 in the African trypanosome.
Bottom Line: Although HAT3 promoted chromosome-internal recombination, it suppressed subtelomeric VSG recombination, and these locus-specific effects were mediated through differential production of ssDNA by DNA resection; HAT3 promoted chromosome-internal resection but suppressed subtelomeric resection.HAT3 also promoted resection at a second chromosome-internal locus comprising tandem-duplicated genes.HAT3 promotes ssDNA formation and recombination at chromosome-internal sites but has the opposite effect at a subtelomeric VSG.
Affiliation: Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK.Show MeSH
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Mentions: We next sought the mechanism by which HAT3 and SIR2rp1 differentially control DNA repair at chromosome-internal and subtelomeric loci. Since DNA resection to generate ssDNA is required for RAD51-focus assembly at the site of the break, we monitored the kinetics of ssDNA accumulation over time adjacent to breaks in the INT and TEL strains (Figure 5). In INT cells, ssDNA accumulates adjacent to a break at the chromosome-internal locus 12 h after induction and declines thereafter (Figure 5A and B), as also described previously (10). In contrast, and consistent with the defects in RAD51-focal assembly and disassembly (Figure 2B and C), ssDNA fails to accumulate in INThat3 cells, and persists in INTsir2rp1 cells (Figure 5A and B).
Affiliation: Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK.