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| DESTABILIZATION OF TRACTS OF SIMPLE REPETITIVE DNA IN YEAST BY MUTATIONS AFFECTING DNA MISMATCH REPAIR |
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| Author(s): STRAND M, PROLLA TA, LISKAY RM, PETES TD |
| Source: NATURE Volume: 365 Issue: 6443 Pages: 274-276 Published: SEP 16 1993 |
| Times Cited: 759 References: 21 |
| Abstract: The genomes of all eukaryotes contain tracts of DNA in which a single base or a small number of bases is repeated. Expansions of such tracts have been associated with several human disorders including the fragile X syndrome1. In addition, simple repeats are unstable in certain forms of colorectal cancer, suggesting a defect in DNA replication or repair2-4. We show here that mutations in any three yeast genes involved in DNA mismatch repair (PMS1, MLH1 and MSH2) lead to 100- to 700-fold increases in tract instability, whereas mutations that eliminate the proof-reading function of DNA polymerases have little effect. The meiotic stability of the tracts is similar to the mitotic stability. Th results suggest that tract instability is associated with DNA polymerases slipping during replication, and that some types of colorectal cancer may reflect mutations in genes involved in DNA mismatch repair. |
| Document Type: Article |
| Language: English |
| Reprint Address: STRAND, M (reprint author), UNIV N CAROLINA, DEPT BIOL, CHAPEL HILL, NC 27599 USA |
Addresses:
1. UNIV N CAROLINA, CURRICULUM GENET & MOLEC BIOL, CHAPEL HILL, NC 27599 USA
2. YALE UNIV, SCH MED, DEPT MOLEC BIOPHYS & BIOCHEM, NEW HAVEN, CT 06510 USA
3. YALE UNIV, SCH MED, DEPT THERAPEUT RADIOL, NEW HAVEN, CT 06510 USA |
| Publisher: MACMILLAN MAGAZINES LTD, PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: LX471 |
| ISSN: 0028-0836 |
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