Multiple pathways regulate the repair of double-strand breaks (DSBs) to suppress potentially dangerous ectopic recombination. Both sequence and chromatin context are thought to influence pathway choice between non-homologous end-joining (NHEJ) and homology-driven recombination. To test the effect of repetitive sequences on break processing, we have inserted TG-rich repeats on one side of an inducible DSB at the budding yeast MAT locus on chromosome III. Five clustered RAP1 sites within a break-proximal TG repeat are sufficient to block Mre11-Rad50-Xrs2 recruitment, impair resection, and favor elongation by telomerase. The two sides of the break lose end-to-end tethering and show enhanced, uncoordinated movement. Only the TG-free side is resected and shifts to the nuclear periphery. In contrast to persistent DSBs without TG repeats that are repaired by imprecise NHEJ, nearly all survivors of repeat-proximal DSBs repair the break by a homology-driven, non-reciprocal translocation from ChrIII-R to ChrVII-L. This suppression of imprecise NHEJ at TG-repeat-flanked DSBs requires the ULS1 translocase activity.

• PMID: 30184497
• DOI full text
• PubMed
• PubTator

Reference Type

Journal Article | Research Support, Non-U.S. Gov't

Authors

Marcomini I, Shimada K, Delgoshaie N, Yamamoto I, Seeber A, Cheblal A, Horigome C, Naumann U, Gasser SM

Primary Lit For

SIR4 | RIF1 | MPS3 | RAD51 | MRE11 | RAD50 | SLX5 | POL32 | RAD59 | ULS1 | RAD52 | ... Show allYKU70 | EXO1 | SLX8 | NFI1 | EST2 | RAP1 | DNL4 Show fewer

Additional Lit For

Review For