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职业迁徙
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My lab uses a combination of genetic and biochemical methods to study (1) telomere structure and replication and (2) replication fork progression. We work mainly in budding and fission yeasts with occasional forays into mammalian systems. Major accomplishments include:
Ciliate termini and YACs: We were the first to construct and characterize a linear artificial chromosome (YAC) (Dani and Zakian 1983 PNAS). In this and subsequent work (Pluta et al., 1984 PNAS), we were one of two groups to use ciliate telomeres to generate linear yeast episomes, a strategy that began the molecular era of yeast telomere biology.
Single strand telomere binding proteins: We isolated and characterized the first single-strand, sequence specific telomere DNA binding protein, the prototype of Pot1, from ciliates (Gottschling and Zakian 1986 Cell). In vitro, the heterodimeric complex is sufficient to distinguish authentic telomeres from DNA ends and to protect them from degradation. We were one of two groups to demonstrate that Cdc13 is the yeast functional equivalent of the ciliate G-strand binding protein (Lin and Zakian 1996 PNAS) and the first to show that it is telomere associated in vivo (Bourns et al., 1998 Mol. Cell. Biol; Tsukamoto 2001 Current Biol). Using genetic and biochemical approaches, we demonstrated that Cdc13 and the telomerase subunit Est1 interact directly, an interaction that is sufficient to bring telomerase to DNA ends in vitro (Qi and Zakian 2000 Genes and Develop.; Wu and Zakian 2011 PNAS). This association is cell cycle regulated, occurring in late S/G2 phase and defines one of the two pathways for recruiting telomerase to telomeres (Taggart et al., 2002 Science). In fission yeast the shelterin-like protein Ccq1 has a Cdc13-like function in recruiting telomerase, again via interaction with Est1 (Webb and Zakian 2012 Genes & Develop.).
Ciliate termini and YACs: We were the first to construct and characterize a linear artificial chromosome (YAC) (Dani and Zakian 1983 PNAS). In this and subsequent work (Pluta et al., 1984 PNAS), we were one of two groups to use ciliate telomeres to generate linear yeast episomes, a strategy that began the molecular era of yeast telomere biology.
Single strand telomere binding proteins: We isolated and characterized the first single-strand, sequence specific telomere DNA binding protein, the prototype of Pot1, from ciliates (Gottschling and Zakian 1986 Cell). In vitro, the heterodimeric complex is sufficient to distinguish authentic telomeres from DNA ends and to protect them from degradation. We were one of two groups to demonstrate that Cdc13 is the yeast functional equivalent of the ciliate G-strand binding protein (Lin and Zakian 1996 PNAS) and the first to show that it is telomere associated in vivo (Bourns et al., 1998 Mol. Cell. Biol; Tsukamoto 2001 Current Biol). Using genetic and biochemical approaches, we demonstrated that Cdc13 and the telomerase subunit Est1 interact directly, an interaction that is sufficient to bring telomerase to DNA ends in vitro (Qi and Zakian 2000 Genes and Develop.; Wu and Zakian 2011 PNAS). This association is cell cycle regulated, occurring in late S/G2 phase and defines one of the two pathways for recruiting telomerase to telomeres (Taggart et al., 2002 Science). In fission yeast the shelterin-like protein Ccq1 has a Cdc13-like function in recruiting telomerase, again via interaction with Est1 (Webb and Zakian 2012 Genes & Develop.).
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Microbial cellno. 9 (2020): 250-254
Carol W. Greider,Nancy Hopkins,Joan A. Steitz,Angelika Amon, David J. Asai,Ben A. Barres,Brenda Bass,Bonnie L. Bassler,R. J. Birgeneau,Pamela J. Björkman,Michael Botchan,Joan S. Brugge,Tom Cech,Rita R. Colwell,Nancy L. Craig, Titia de Lange,Michael B. Eisen,Susan Gottesman,Rachel Green,Jo Handelsman,Judith Kimble,Mary‐Claire King,Ruth Lehmann,Eve Marder, Dyche Mullins,Erin K. O’Shea, Sandra L. Schmid,Géraldine Seydoux,Allan C. Spradling,Gisela Storz,Jack W. Szostak,Alice Telesnitsky, Shirley M. Tilghman,Robert Tjian, Ronald D. Vale,Cynthia Wolberger,Virginia A. Zakian
Scienceno. 6356 (2017): 1105-1106
Carol Greider,Nancy Hopkins,Joan Steitz,Angelika Amon,David Asai,Ben Barres,Brenda Bass,Bonnie Bassler,Robert Birgeneau,Pamela Bjorkman,Michael Botchan,Joan Brugge,Tom Cech,Rita Colwell,Nancy Craig,Titia Delange,Michael Eisen, Susan Gottesman,Rachel Green,Jo Handelsman,Judith Kimble,Mary-Claire King,Ruth Lehmann,Eve Marder,Dyche Mullins,Erin O'Shea,Sandra Schmid,Geraldine Seydoux,Allan Spradling,Gisela Storz,Jack Szostak,Alice Telesnitsky,Shirley Tilghman,Robert Tjian,Ronald Vale,Cynthia Wolberger,Virginia Zakian
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#Papers: 191
#Citation: 20934
H-Index: 69
G-Index: 144
Sociability: 6
Diversity: 0
Activity: 0
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