Both CAG repeats and inverted DNA repeats stimulate spontaneous unequal sister-chromatid exchange in Saccharomyces cerevisiae.
Genomic regions containing trinucleotide repeats (TNRs) are highly unstable, as the repeated sequences exhibit a high rate of mutational change, in which they undergo either a contraction or an expansion of repeat numbers. Although expansion of TNRs is associated with several human genetic diseases, the expansion mechanism is poorly understood. Extensive studies in model organisms have indicated that instability of TNRs occurs by several mechanisms, including replication slippage, DNA repair and recombination. In all models, the formation of secondary structures by disease-associated TNRs is a critical step in the mutation process. In this report, we demonstrate that TNRs and inverted repeats (IRs) both of which have the potential to form secondary structures in vivo, increase spontaneous unequal sister-chromatid exchange (SCE) in vegetatively growing yeast cells. Our results also show that TNR-mediated SCE events are independent of RAD50, MRE11 and RAD51, whereas IR-stimulated SCEs are dependent on the RAD52 epistasis-group genes. We propose that many TNR expansion mutations occur by SCE.
Nag
Dilip K
DK
Molecular Genetics Program, Center for Medical Sciences, Wadsworth Center, 150 New Scotland Avenue, Albany, NY 12208, USA. dilip.nag@wadsworth.org
Suri
Manisha
M
Stenson
Erin K
EK
D004247:DNA / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000502:physiology; D004706:Endodeoxyribonucleases / Q000502:physiology; D005090:Exodeoxyribonucleases / Q000502:physiology; D051135:Rad51 Recombinase; D051721:Rad52 DNA Repair and Recombination Protein; D012091:Repetitive Sequences, Nucleic Acid; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology; D012854:Sister Chromatid Exchange; D018911:Trinucleotide Repeats
D004268:DNA-Binding Proteins; C086930:RAD50 protein, S cerevisiae; C497197:RAD52 protein, S cerevisiae; D051721:Rad52 DNA Repair and Recombination Protein; D029701:Saccharomyces cerevisiae Proteins; D004247:DNA; C495151:RAD51 protein, S cerevisiae; D051135:Rad51 Recombinase; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases; C094191:MRE11 protein, S cerevisiae