Most Significant Lab Publications
Construction and analysis of first linear artificial chromosomes: Dani GM and Zakian VA. (1983) Mitotic and meiotic stability of linear plasmids in yeast. Proc. Natl. Acad. Sci. USA 80: 3406-‐3410.
Isolation and characterization of first telomeric G-‐strand binding protein, the Pot1 prototype: Gottschling DE and Zakian VA. (1986) Telomere Proteins: Specific recognition and protection of natural termini of Oxytricha macronuclear DNA. Cell 47: 195-‐205.
First demonstration of lengthening of canonical telomeric repeats by recombination: Pluta AF and Zakian VA. (1989) Recombination occurs during telomere formation in yeast. Nature 337: 429-‐ 433; Wang S-‐S and Zakian VA. (1990) Telomere-‐telomere recombination provides an express pathway for telomere acquisition. Nature 345: 456-‐458.
Firstdescriptionoftelomericsilencingin yeast: Gottschling DE, Aparicio DM, Billington BL and Zakian VA. (1990) Position effect at S. cerevisiae telomeres: reversible repression of Pol II transcription. Cell 63: 751-‐762.
First demonstration of telomere binding of a sequence-‐specific duplex telomere binding protein and its importance for telomere length control: Conrad MN, Wright J, Wolf A and Zakian VA. (1990) RAP1 protein interacts with yeast telomeres in vivo: Overproduction alters telomere structure and decreases chromosome stability. Cell 63: 739-‐750.
Discovery of C-‐strand degradation as a normal event in telomere processing: Wellinger RJ, Wolf A and Zakian VA. (1993) Saccharomyces telomeres acquire single-‐strand TG1-‐3 tails late in S phase. Cell 72: 51-‐60; Wellinger RJ, Wolf AJ, and Zakian VA. (1993) Origin activation and formation of single- strand TG1-3 tails occur sequentially in late S phase on a linear plasmid. Mol. Cell. Biol. 13:4057-4065. Wellinger RJ, Etier K, Labreque P and Zakian VA. (1996) Evidence for a new step in telomere maintenance. Cell 85: 423-‐433.
Demonstration that loss of a single telomere (or presence of a single double strand break) elicits a robust cell cycle arrest that can be overcome (“adaptation”) such that a chromosome without a telomere can persist for many generations: Sandell LL and Zakian VA. (1993) Loss of a yeast telomere: arrest, recovery and chromosome loss. Cell 75: 729-‐739.
Identification of the Pif1 DNA helicase as a negative regulator of telomerase that acts by evicting telomerase from DNA ends: Schulz VP and Zakian VA. (1994) The Saccharomyces PlFl DNA helicase inhibits telomere elongation and de novo telomere formation Cell 76: 145-‐155; Zhou J-‐Q, Monson EK, Teng S-‐C, Schulz VP, and Zakian VA. (2000) Pif1p helicase, a catalytic inhibitor of telomerase in yeast. Science. 289: 771-‐774. Boulé JB, Vega LR, and Zakian VA. (2005) The yeast Pif1p helicase removes telomerase from telomeric DNA. Nature 438: 57-‐61.
Determination that gene conversion between tracts of telomeric repeats can maintain yeast telomeres in the absence of telomerase, a process similar to ALT in mammalian cells: Teng SC and Zakian VA. (1999) Telomere-‐telomere recombination is an efficient bypass pathway for telomere maintenance in Saccharomyces cerevisiae. Mol. Cell. Biol. 19: 8083-‐8093; Teng S-‐C, Chang J, McCowan B and Zakian VA. (2000) Telomerase-‐independent lengthening of yeast telomeres occurs by an abrupt Rad50p-‐dependent, Rif-‐inhibited recombinational process. Mol. Cell. 6: 947-‐952.
Discovery of Pif1 family DNA helicases, Rrm3 (budding yeast) and Pfh1 (fission yeast) as enzymatic promoters of replication fork progression past stable protein complexes: Ivessa AS, Zhou J-‐Q, and Zakian VA. (2000) The Saccharomyces Pif1p DNA helicase and the highly related Rrm3p have opposite effects on replication fork progression in ribosomal DNA. Cell. 100: 479-‐489; Ivessa AS, Zhou J-‐Q, Schulz VP, Monson EK, and Zakian VA. (2002) Saccharomyces Rrm3p, a 5’ to 3’ DNA helicase that promotes replication fork progression through telomeric and sub-‐telomeric DNA. Genes Dev. 16: 1383-‐1396; Ivessa AS, Lenzmeier BA, Bessler JB, Goudsouzian LK, Schnakenberg SL and Zakian VA. (2003) The S. cerevisiae helicase Rrm3p facilitates replication past non-‐histone protein-‐DNA complexes. Mol. Cell. 12: 1525-‐1536; Torres JZ, Bessler JB, and Zakian VA. (2004) Local chromatin structure at the ribosomal DNA causes replication fork pausing and genome instability in the absence of the S. cerevisiae DNA helicase Rrm3p. Genes Dev. 18: 498-503; Azvolinsky A, Giresi PG, Lieb JD, Zakian VA. (2009) Highly transcribed RNA polymerase II genes are impediments to replication fork progression in S.cerevisiae. Mol. Cell 34: 722-‐734; Sabouri N, McDonald K, Webb CJ, Cristea I, and Zakian VA. (2012) DNA replication through hard-‐to-‐replicate sites, including both highly transcribed RNA Pol II and Pol III genes, requires the S. pombe Pfh1 helicase. Genes Dev. 26: 581-‐593; McDonald, KR, Sabouri, N, Webb, CJ, and Zakian, VA (2014) Pfh1 is a positive regulator of telomere replication and telomere length. DNA Repair 24:80-6.
Discovery of Pif1 family helicases from bacteria to humans as promoting replication past and suppressing DNA damage at G-‐quadruplex motifs: Paeschke K, Capra JA, and Zakian VA. (2011) DNA replication through G-‐quadruplex motifs is promoted by the S. cerevisiae Pif1 DNA helicase. Cell 145: 678-‐691; Paeschke K, Bochman ML, Garcia PD, Cejka P, Friedman KL, Kowalczykowski SC, and Zakian VA. (2013) Pif1 helicases from bacteria to humans suppress genome instability at G-‐quadruplex DNA motifs. Nature 497:458-‐462; Sabouri, N, Capra JA, and Zakian VA (2014) The essential S. pombe Pfh1 DNA helicase promotes fork movement past G-‐quadruplex motifs to prevent DNA damage. BMC Biology 12:101; Zhou R, Zhang J, Bochman, ML, Zakian VA and Ha TJ (2014) Periodic DNA patrolling underlies diverse functions of Pif1 on R-‐loops and G-‐rich DNA. eLIFE. 3:e02190.
Determination of mechanistic basis for cell cycle regulated recruitment of budding yeast telomerase to telomeres: Taggart AKP, Teng S-‐C, and Zakian VA. (2002) Est1p as a cell cycle regulated activator of telomere-‐bound telomerase. Science. 297: 1023-‐1026; Fisher TS, Taggart AKP, and Zakian VA. (2004) Cell cycle-‐dependent regulation of yeast telomerase by Ku. Nat. Struct. Mol. Biol. 11: 1198-‐1205; Tuzon CT, Wu Y, Chan A, and Zakian VA. (2011) The S. cerevisiae telomerase subunit Est3 binds telomeres in a cell cycle and Est1 dependent manner and interacts directly with Est1 PLoS Genet. 7: e1002060; Wu Y and Zakian VA. (2011) The telomeric Cdc13 protein interacts directly with the telomerase subunit Est1 to bring it to telomeric DNA ends in vitro. PNAS 108: 20362-‐20369; Lin KW, McDonald KR, Guise AJ, Chan A, Cristea IM, Zakian VA (under review). Proteomics of budding yeast telomerase: the telomerase associated Cdc48-‐Npl4-‐Ufd1 complex regulates Est1 abundance and telomere length.
Elucidating mechanisms for preferential lengthening of short telomeres in budding yeast: Sabourin M, Tuzon, CT, and Zakian VA. (2007) Telomerase and Tel1p preferentially associate with short telomeres in S. cerevisiae. Mol. Cell 27: 550-‐561; McGee JS, Phillips JA, Chan A, Sabourin M, Paeschke K and Zakian VA. (2010) Reduced Rif2 and lack of Mec1 target short telomeres for elongation rather than double-‐strand break repair. Nat. Struct. Molec. Biol. 17: 1438-‐1445; Phillips JA, Chan, A, Paeschke K, and Zakian VA (under review) The Pif1 helicase, a negative regulator of telomerase, acts preferentially at long telomeres.
Isolation of fission yeast telomerase RNA and determination of its functional domains: Webb CJ and Zakian VA. (2008) Identification and characterization of the Schizosaccharomyces pombe TER1 telomerase RNA. Nat. Struct. Mol. Biol. 15: 34-‐42; Webb CJ and Zakian VA. (2012). Schizosaccharomyces pombe Ccq1 and TER1 bind the 14-‐3-‐3-‐like domain of Est1, which promotes and stabilizes telomerase-‐telomere association. Genes Dev. 26: 82-‐91; Webb CJ and Zakian VA (under review) The telomerase RNA stem terminus element affects template boundary element function, telomere sequence and shelterin binding.