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Recombination‐induced CAG trinucleotide repeat expansions in yeast involve the MRE11–RAD50–XRS2 complex
Author(s) -
Richard GuyFranck,
Goellner Geoffrey M.,
McMurray Cynthia T.,
Haber James E.
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.10.2381
Subject(s) - trinucleotide repeat expansion , biology , rad50 , dna , dna repair , recombination , gene conversion , genetics , microbiology and biotechnology , homologous recombination , gene , branch migration , dna replication , dna binding protein , holliday junction , allele , transcription factor
Recombination induced by double‐strand breaks (DSBs) in yeast leads to a higher proportion of expansions to contractions than does replication‐associated tract length changes. Expansions are apparently dependent on the property of the repeat array to form hairpins, since DSB repair of a CAA 87 repeat induces only contractions of the repeat sequence. DSB‐repair efficiency is reduced by 40% when DNA synthesis must traverse a CAG 98 array, as compared with a CAA 87 array. These data indicate that repair‐ associated DNA synthesis is inhibited by secondary structures formed by CAG 98 and that these structures promote repeat expansions during DSB repair. Overexpression of Mre11p or Rad50p suppresses the inhibition of DSB repair by CAG 98 and significantly increases the average size of expansions found at the recipient locus. Both effects are dependent on the integrity of the Mre11p–Rad50p–Xrs2p complex. The Mre11 complex thus appears to be directly involved in removing CAG or CTG hairpins that arise frequently during DNA synthesis accompanying gene conversion of these trinucleotide repeats.