Affiliation:
1. Department of Pharmacology, Division of Cellular and Molecular Medicine, University of California, San Diego, La Jolla 92093-0651, USA.
Abstract
To investigate the relationship between the DNA replication apparatus and the control of telomere length, we examined the effects of several DNA replication mutations on telomere length in Saccharomyces cerevisiae. We report that a mutation in the structural gene for the large subunit of DNA replication factor C (cdc44/rfc1) causes striking increases in telomere length. A similar effect is seen with mutations in only one other DNA replication gene: the structural gene for DNA polymerase alpha (cdc17/pol1) (M.J. Carson and L. Hartwell, Cell 42:249-257, 1985). For both genes, the telomere elongation phenotype is allele specific and appears to correlate with the penetrance of the mutations. Furthermore, fluorescence-activated cell sorter analysis reveals that those alleles that cause elongation also exhibit a slowing of DNA replication. To determine whether elongation is mediated by telomerase or by slippage of the DNA polymerase, we created cdc17-1 mutants carrying deletions of the gene encoding the RNA component of telomerase (TLC1). cdc17-1 strains that would normally undergo telomere elongation failed to do so in the absence of telomerase activity. This result implies that telomere elongation in cdc17-1 mutants is mediated by the action of telomerase. Since DNA replication involves transfer of the nascent strand from polymerase alpha to replication factor C (T. Tsurimoto and B. Stillman, J. Biol. Chem. 266:1950-1960, 1991; T. Tsurimoto and B. Stillman, J. Biol. Chem. 266:1961-1968, 1991; S. Waga and B. Stillman, Nature [London] 369:207-212, 1994), one possibility is that this step affects the regulation of telomere length.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
Reference47 articles.
1. Ausubel F. M. R. Brent R. E. Kingston D. D. Moore J. G. Seidman J. A. Smith and K. Struhl (ed.). 1988. Current protocols in molecular biology. Greene Publishing Associates and Wiley Interscience New York.
2. The molecular structure of centromeres and telomeres. Annu;Blackburn E. H.;Rev. Biochem.,1984
3. Structure and function of telomeres;Blackburn E. H.;Nature (London),1991
4. Functional characterization and developmental regulation of mouse telomerase RNA;Blasco M. A.;Science,1995
5. Telomerase activity in normal and malignant hematopoietic cells;Broccoli D.;Proc. Natl. Acad. Sci. USA,1995
Cited by
82 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献