Journal ArticleDOI
Destabilization of tracts of simple repetitive DNA in yeast by mutations affecting DNA mismatch repair
TLDR
It is shown that mutations in any three yeast genes involved in DNA mismatch repair lead to 100- to 700-fold increases in tract instability, whereas mutations that eliminate the proof-reading function of DNA polymerases have little effect.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 syndrome. In addition, simple repeats are unstable in certain forms of colorectal cancer, suggesting a defect in DNA replication or repair. 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. These 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.read more
Citations
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Journal ArticleDOI
Lessons from Hereditary Colorectal Cancer
TL;DR: The authors are grateful to the members of their laboratories for their contributions to the reviewed studies and to F. Giardiello and S. Hamilton for photographs of colorectal lesions.
Journal ArticleDOI
Genetic instabilities in human cancers
TL;DR: There is now evidence that most cancers may indeed be genetically unstable, but that the instability exists at two distinct levels, and recognition and comparison of these instabilities are leading to new insights into tumour pathogenesis.
Journal ArticleDOI
The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer.
Richard Fishel,Mary Kay Lescoe,M.R.S. Rao,Neal G. Copeland,Nancy A. Jenkins,Judy Garber,Michael F. Kane,Richard D. Kolodner +7 more
TL;DR: Data and reports indicating that S. cerevisiae msh2 mutations cause an instability of dinucleotide repeats like those associated with H NPCC suggest that hMSH2 is the HNPCC gene.
Journal ArticleDOI
Damage to DNA by reactive oxygen and nitrogen species: role in inflammatory disease and progression to cancer.
Helen Wiseman,Barry Halliwell +1 more
TL;DR: ROS and RNS could contribute to the initiation of cancer, in addition to being important in the promotion and progression phases, as evidence is growing that antioxidants may prevent or delay the onset of some types of cancer.
Journal ArticleDOI
Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer
Fredrick S. Leach,Nicholas C. Nicolaides,Nickolas Papadopoulos,Bo Liu,Jin Jen,Ramon Parsons,Päivi Peltomäki,Pertti Sistonen,Lauri A. Aaltonen,Minna Nyström-Lahti,Xin Yuan Guan,Ji Zhang,Paul S. Meltzer,Jing Wei Yu,Fa Ten Kao,David J. Chen,Karen M. Cerosaletti,R. E. Keith Fournier,Sean Todd,Tracey B. Lewis,Robin J. Leach,Susan L. Naylor,Jean Weissenbach,Jukka-Pekka Mecklin,Heikki Järvinen,Gloria M. Petersen,Stanley R. Hamilton,Jane Green,Jeremy R. Jass,Patrice Watson,Henry T. Lynch,Jeffrey M. Trent,Albert de la Chapelle,Kenneth W. Kinzler,Bert Vogelstein +34 more
TL;DR: Somatic as well as germline mutations of the gene were identified in RER+ tumor cells, and this mutS homolog is likely to be responsible for HNPCC.
References
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Journal ArticleDOI
Mutations of bacteria from virus sensitivity to virus resistance
Salvador E. Luria,Max Delbrück +1 more
TL;DR: This article reported Luria and Delbruck's breakthrough study in which they established that viruses do not induce mutations in bacteria, but that virus-resisting mutations are spontaneous.
Journal ArticleDOI
Microsatellite instability in cancer of the proximal colon
TL;DR: Colorectal tumor DNA was examined for somatic instability at (CA)n repeats on human chromosomes 5q, 15q, 17p, and 18q, and this instability was significantly correlated with the tumor's location in the proximal colon and with increased patient survival and loss of heterozygosity.
Journal ArticleDOI
Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis
TL;DR: It is shown that 12 per cent of colorectal carcinomas carry somatic deletions in poly(dA . dT) sequences and other simple repeats, and it is concluded that these mutations reflect a previously undescribed form of carcinogenesis in the colon mediated by a mutation in a DNA replication factor resulting in reduced fidelity for replication or repair (a 'mutator mutation').
Journal ArticleDOI
Clues to the pathogenesis of familial colorectal cancer
Lauri A. Aaltonen,Päivi Peltomäki,Fredrick S. Leach,Pertti Sistonen,Lea Pylkkänen,Jukka-Pekka Mecklin,Heikki Järvinen,Steven M. Powell,Jin Jen,Stanley R. Hamilton,Gloria M. Petersen,Kenneth W. Kinzler,Bert Vogelstein,Albert de la Chapelle +13 more
TL;DR: Molecular features of "familial" cancers were compared with those of sporadic colon cancers, and a mechanism for familial tumorigenesis different from that mediated by classic tumor suppressor genes is suggested.
Journal ArticleDOI
A positive selection for mutants lacking orotidine-5'-phosphate decarboxylase activity in yeast: 5-fluoro-orotic acid resistance.
TL;DR: Mutations at the URA3 locus of Saccharomyces cerevisiae can be obtained by a positive selection, based on the loss of orotidine-5′-phosphate decarboxylase activity, and seems applicable to a variety of eucaryotic and procaryotic cells.
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Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer
Fredrick S. Leach,Nicholas C. Nicolaides,Nickolas Papadopoulos,Bo Liu,Jin Jen,Ramon Parsons,Päivi Peltomäki,Pertti Sistonen,Lauri A. Aaltonen,Minna Nyström-Lahti,Xin Yuan Guan,Ji Zhang,Paul S. Meltzer,Jing Wei Yu,Fa Ten Kao,David J. Chen,Karen M. Cerosaletti,R. E. Keith Fournier,Sean Todd,Tracey B. Lewis,Robin J. Leach,Susan L. Naylor,Jean Weissenbach,Jukka-Pekka Mecklin,Heikki Järvinen,Gloria M. Petersen,Stanley R. Hamilton,Jane Green,Jeremy R. Jass,Patrice Watson,Henry T. Lynch,Jeffrey M. Trent,Albert de la Chapelle,Kenneth W. Kinzler,Bert Vogelstein +34 more