Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (23)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Boyer, J. C.
Right arrow Articles by Farber, R. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Boyer, J. C.
Right arrow Articles by Farber, R. A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Molecular Genetics, 2002, Vol. 11, No. 6 707-713
© 2002 Oxford University Press

Sequence dependent instability of mononucleotide microsatellites in cultured mismatch repair proficient and deficient mammalian cells

Jayne C. Boyer1,+, Nazumi A. Yamada1, C. Natalia Roques1, Stephanie B. Hatch2, Kevin Riess1 and Rosann A. Farber1,2,3

1Department of Pathology and Laboratory Medicine, 2Curriculum in Genetics and Molecular Biology and 3Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA

We have measured the mutation rates of G17 and A17 repeat sequences in cultured mammalian cells with and without mismatch repair and have compared these rates to those of a (CA)17 repeat sequence. Plasmids containing microsatellites that disrupt the reading frame of a downstream neomycin-resistance gene were introduced into the cells by transfection and revertants were selected using the neomycin analog G418. Comparison of mutation rates within cell lines showed that the mutation rates of A17 and (CA)17 sequences were similar in the mismatch repair proficient cells, but the mutation rate of G17 was significantly higher than that of either A17 or (CA)17. In the mismatch repair deficient cells, the G17 and (CA)17 mutation rates were similar and were significantly higher than the A17 rate. PCR analysis of the mutants showed that 1 bp insertions predominated in both mononucleotide repeats in the mismatch repair proficient cells; in mismatch repair deficient cells, 2 bp deletions were the most common mutation in the A17 sequence, but 1 bp insertions and 2 bp deletions were equally represented in the G17 sequence. These results indicate that a G17 repeat is less stable than an A17 repeat in both mismatch repair proficient and mismatch repair deficient mammalian cells. This observation implies that the replication fidelity is lower in G17 repeats.

+ To whom correspondence should be addressed. Tel: +1 919 966 6921; Fax: +1 919 966 0717; Email: jayne_boyer@med.unc.edu


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Proc. Natl. Acad. Sci. USAHome page
J. J. Salk, S. J. Salipante, R. A. Risques, D. A. Crispin, L. Li, M. P. Bronner, T. A. Brentnall, P. S. Rabinovitch, M. S. Horwitz, and L. A. Loeb
Clonal expansions in ulcerative colitis identify patients with neoplasia
PNAS, December 8, 2009; 106(49): 20871 - 20876.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
A. L. Seyfert, M. E. A. Cristescu, L. Frisse, S. Schaack, W. K. Thomas, and M. Lynch
The Rate and Spectrum of Microsatellite Mutation in Caenorhabditis elegans and Daphnia pulex
Genetics, April 1, 2008; 178(4): 2113 - 2121.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
S. J. Salipante, J. M. Thompson, and M. S. Horwitz
Phylogenetic Fate Mapping: Theoretical and Experimental Studies Applied to the Development of Mouse Fibroblasts
Genetics, February 1, 2008; 178(2): 967 - 977.
[Abstract] [Full Text] [PDF]

Home page
 Genome ResHome page
Y. D. Kelkar, S. Tyekucheva, F. Chiaromonte, and K. D. Makova
The genome-wide determinants of human and chimpanzee microsatellite evolution
Genome Res., January 1, 2008; 18(1): 30 - 38.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
H. Sammalkorpi, P. Alhopuro, R. Lehtonen, J. Tuimala, J.-P. Mecklin, H. J. Jarvinen, J. Jiricny, A. Karhu, and L. A. Aaltonen
Background Mutation Frequency in Microsatellite-Unstable Colorectal Cancer
Cancer Res., June 15, 2007; 67(12): 5691 - 5698.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
S. J. Salipante and M. S. Horwitz
Phylogenetic fate mapping
PNAS, April 4, 2006; 103(14): 5448 - 5453.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
P. Cejka, G. Marra, C. Hemmerle, E. Cannavo, Z. Storchova, and J. Jiricny
Differential Killing of Mismatch Repair-Deficient and -Proficient Cells: Towards the Therapy of Tumors with Microsatellite Instability
Cancer Res., December 1, 2003; 63(23): 8113 - 8117.
[Abstract] [Full Text] [PDF]

Home page
 Plant Physiol.Home page
J. M. Leonard, S. R. Bollmann, and J. B. Hays
Reduction of Stability of Arabidopsis Genomic and Transgenic DNA-Repeat Sequences (Microsatellites) by Inactivation of AtMSH2 Mismatch-Repair Function
Plant Physiology, September 1, 2003; 133(1): 328 - 338.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
H. Gragg, B. D. Harfe, and S. Jinks-Robertson
Base Composition of Mononucleotide Runs Affects DNA Polymerase Slippage and Removal of Frameshift Intermediates by Mismatch Repair in Saccharomyces cerevisiae
Mol. Cell. Biol., December 15, 2002; 22(24): 8756 - 8762.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
N. A. Yamada and R. A. Farber
Induction of a Low Level of Microsatellite Instability by Overexpression of DNA Polymerase {beta}
Cancer Res., November 1, 2002; 62(21): 6061 - 6064.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.