Requirement of the yeast RTH1 5' to 3' exonuclease for the stability of simple repetitive DNA.
Simple repetitive DNA sequences are unstable in human colorectal cancers and a variety of other cancers. Mutations in the DNA mismatch repair genes MSH2, MLH1, and PMS1 result in elevated rates of spontaneous mutation and cause a marked increase in the instability of simple repeats. Compared with the wild type, a null mutation in the yeast RTH1 gene, which encodes a 5' to 3' exonuclease, was shown to increase the rate of instability of simple repetitive DNA by as much as 280 times and to increase the spontaneous mutation rate by 30 times. Epistasis analyses were consistent with the hypothesis that this RTH1-encoded nuclease has a role in the MSH2-MLH-1-PMS1 mismatch repair pathway.
Johnson
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Center for Molecular Science, University of Texas Medical Branch, Galveston 77555-1061, USA.
Kovvali
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Prakash
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Prakash
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D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004260:DNA Repair; D004271:DNA, Fungal / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D043211:Exodeoxyribonuclease V; D005090:Exodeoxyribonucleases / Q000235:genetics* / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics; D005800:Genes, Fungal; D000070957:MutL Protein Homolog 1; D000070956:MutL Proteins; D051718:MutS Homolog 2 Protein; D009154:Mutation; D009363:Neoplasm Proteins; D012091:Repetitive Sequences, Nucleic Acid; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C088859:MLH1 protein, S cerevisiae; D009363:Neoplasm Proteins; C088858:PMS1 protein, S cerevisiae; C088996:PMS1 protein, human; D029701:Saccharomyces cerevisiae Proteins; D005090:Exodeoxyribonucleases; D043211:Exodeoxyribonuclease V; C489751:MSH2 protein, S cerevisiae; D000070957:MutL Protein Homolog 1; D000070956:MutL Proteins; D051718:MutS Homolog 2 Protein