Coordinate regulation of G- and C strand length during new telomere synthesis.
We have used the ciliate Euplotes to study the role of DNA polymerase in telomeric C strand synthesis. Euplotes provides a unique opportunity to study C strand synthesis without the complication of simultaneous DNA replication because millions of new telomeres are made at a stage in the life cycle when no general DNA replication takes place. Previously we showed that the C-strands of newly synthesized telomeres have a precisely controlled length while the G-strands are more heterogeneous. This finding suggested that, although synthesis of the G-strand (by telomerase) is the first step in telomere addition, a major regulatory step occurs during subsequent C strand synthesis. We have now examined whether G- and C strand synthesis might be regulated coordinately rather than by two independent mechanisms. We accomplished this by determining what happens to G- and C strand length if C strand synthesis is partially inhibited by aphidicolin. Aphidicolin treatment caused a general lengthening of the G-strands and a large increase in C strand heterogeneity. This concomitant change in both the G- and C strand length indicates that synthesis of the two strands is coordinated. Since aphidicolin is a very specific inhibitor of DNA pol alpha and pol delta, our results suggest that this coordinate length regulation is mediated by DNA polymerase.
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Department of Chemistry, University of Nebraska, Lincoln 68588, USA.
Price
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D000818:Animals; D016590:Aphidicolin / Q000494:pharmacology; D001482:Base Composition; D003001:Cloning, Molecular; D003596:Cytosine; D004261:DNA Replication / Q000187:drug effects; D016054:DNA, Protozoan / Q000096:biosynthesis* / Q000737:chemistry; D004259:DNA-Directed DNA Polymerase / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016812:Euplotes / Q000166:cytology / Q000235:genetics*; D006147:Guanine; D019384:Nucleic Acid Synthesis Inhibitors; D017422:Sequence Analysis, DNA; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000737:chemistry / Q000378:metabolism*
D016054:DNA, Protozoan; D004791:Enzyme Inhibitors; D019384:Nucleic Acid Synthesis Inhibitors; D016590:Aphidicolin; D006147:Guanine; D003596:Cytosine; D019098:Telomerase; D004259:DNA-Directed DNA Polymerase