Genomic deletions and point mutations induced in Saccharomyces cerevisiae by the trinucleotide repeats (GAA¡¤TTC) associated with Friedreich's ataxia

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• 作者：Wei Tang ; Margaret Dominska ; Malgorzata Gawel ; Patricia W. Greenwell ; Thomas D. Petes ; ^{tom.petes@duke.edu}
• 关键词：Friedreich's ataxia ; GAA· ; TTC triplet repeats ; Genome instability ; Mutations ; Saccharomyces cerevisiae
• 刊名：DNA Repair
• 出版年：2013
• 出版时间：1 January, 2013
• 年：2013
• 卷：12
• 期：1
• 页码：10-17
• 全文大小：948 K

文摘

Expansion of certain trinucleotide repeats causes several types of human diseases, and such tracts are associated with the formation of deletions and other types of genetic rearrangements in Escherichia coli, yeast, and mammalian cells. Below, we show that long (230 repeats) tracts of the trinucleotide associated with Friedreich's ataxia (GAA¡¤TTC) stimulate both large (>50 bp) deletions and point mutations in a reporter gene located more than 1 kb from the repetitive tract. Sequence analysis of deletion breakpoints indicates that the deletions reflect non-homologous end joining of double-stranded DNA breaks (DSBs) initiated in the tract. The tract-induced point mutations appear to reflect a different mechanism involving single-strand annealing of DNA molecules generated by DSBs within the tract, followed by filling-in of single-stranded gaps by the error-prone DNA polymerase zeta.