Study of the Regulation of Telomere Replication by Characterizing the Cdc13p Pathway in Yeast
Annual summary rept. 1 Jan-31 Dec 1999
PRINCETON UNIV NJ
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Telomeres are repeated double stranded DNA sequences at chromosome ends with G rich 3-ends G-strand and C rich 5-ends C-strand. Telomerase is the telomere G-strand synthesis enzyme. Recent data suggested that telomere replication might be involved in the origin or progression of cancer and aging. Understanding telomere replication might offer ways for screening drugs against and preventing cancer and aging. The conservation of DNA replication and telomere structure has made yeast a good system to study telomere replication. An essential telomere protein in budding yeast, Cdcl3p, has been proposed to bind telomeres to limit C-strand degradation and to recruit telomerase to telomeres. These steps are necessary for telomere replication. To better understand telomere replication, a two-hybrid assay was used to identify proteins interacting with Cdcl3p. We found Pol1p, the catalytic subunit of DNA polymerase a pol alpha, and Estlp, a telomerase component, interacted with Cdcl3p. These interactions were confirmed by biochemical criteria. Disruption of the Pol1p-Cdcl3p interaction resulted in longer telomeres. Data suggested that the pol a is the C-strand resynthesis enzyme. The balance of the opposite movements of telomerase and Pol a during telomere replication is one of the mechanisms to control telomere length. Cdcl3p is a key protein to control this balance through interaction with Estlp and Pol1p. These data should help us to further understand mammalian telomere replication.
- Medicine and Medical Research