Molecular Cell
Volume 55, Issue 4, 21 August 2014, Pages 615-625
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Article
Frequent Interchromosomal Template Switches during Gene Conversion in S. cerevisiae

https://doi.org/10.1016/j.molcel.2014.06.025Get rights and content
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Highlights

  • Interchromosomal template switches (ICTS) occur in nearly 1% of DSB repair events

  • ICTS is not impaired by heterochromatin

  • Mismatch repair proteins Msh6 and Mlh1 direct strand-repair of heteroduplex DNA

  • The chromatin remodeler Rdh54 is required for ICTS but not simple gene conversion

Summary

Although repair of double-strand breaks (DSBs) by gene conversion is the most accurate way to repair such lesions, in budding yeast there is a 1,000-fold increase in accompanying mutations, including interchromosomal template switches (ICTS) involving highly mismatched (homeologous) ectopic sequences. Although such events are rare and appear at a rate of 2 × 10−7 when template jumps occur between 71% identical sequences, they are surprisingly frequent (0.3% of all repair events) when the second template is identical to the first, revealing the remarkable instability of repair DNA synthesis. With homeologous donors, ICTS uses microhomologies as small as 2 bp. Cells lacking mismatch repair proteins Msh6 and Mlh1 form chimeric recombinants with two distinct patches of microhomology, implying that these proteins are crucial for strand discrimination of heteroduplex DNA formed during ICTS. We identify the chromatin remodeler Rdh54 as the first protein required for template switching that does not affect simple gene conversion.

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