Professor Research Research Interests: Eukaryotic chromosomes terminate with specific structures known as telomeres which permit the complete replication of chromosome ends and which also provide them with a protective "cap." The former role is achieved by the enzyme telomerase, a specialized reverse transcriptase that synthesizes a short DNA sequence directly onto the chromosomal terminus. Full telomeric function is provided by tandem arrays of this short repeat. There is considerable recent excitement in the possibility that loss of telomere function may often be a crucial event in carcinogenesis. Human somatic cells typically have little or no telomerase and display gradual telomere loss; however, most human cancers emerge with high levels of telomerase. My own work is involved with studying telomeres and telomerase in yeasts. I have found that consequences of altered telomere function can include cellular growth senescence, runaway telomere elongation, greatly increased telomeric recombination, and telomere-telomere fusions. Future aims will include identifying and characterizing other components of telomeres and telomerase and determining other roles they may play within cells. Grants: “Recombinational Telomere Maintanance,” NIH“Searching Genomes for their Non-Coding RNAs by their Structure,” NIH Selected Publications Selected Publications: Bechard, L.H., B.D. Butuner, G.J. Peterson, W. McRae, Z. Topcu and M.J. McEachern. 2009. Mutant telomeric repeats in yeast can disrupt the negative regulation of recombination-mediated telomere maintenance and create an Alternative-Lengthening of Telomeres-like phenotype. Mol. Cell. Biol. 29: 626-639. Cesare, A.J., C. Groff-Vindman, S.A. Compton, M.J. McEachern and J.D. Griffith. 2008. Telomere loops and homologous recombination-dependent telomeric circles in a Kluyveromyces lactis telomere mutant strain. Mol. Cell. Biol. 28: 20-29.Hsu, M., M.J. McEachern, T.A. Sankjinou, Y. Tfzati, E. Orr, E.H. Blackburn and N.F. Lue. 2007. Telomerase core components protect Candida telomeres against aberrant overhang accumulation. Proc Natl. Acad. Sci. USA 104: 11682-11687.McEachern, M.J. 2007. Telomeres: Guardians of genomic integrity or double agents of evolution? In: Origins and evolution of telomeres. J. Noseck, L. Tomaska (eds). Landes Bioscience, Eurekah Press. Carter, S. D., S. Iyer, J. Xu, M.J. McEachern and S.U. Astrom. 2007. The role of NHEJ-components in telomere metabolism in Kluyveromyces lactis. Genetics 175: 1035-1045.McEachern, M.J. and J.E. Haber. 2006. Break-induced replication and recombinational telomere elongation in yeast. Ann. Rev. Biochem. 75: 111-135. Natarajan, S., K. Nickles and M.J. McEachern. 2006. Screening for telomeric recombination in wild-type Kluyveromyces lactis. FEMS Yeast Research 6: 442-448.Iyer, S., A.D. Chadha and M.J. McEachern. 2005. A mutation in the STN1 gene triggers an alternative lengthening of telomere-like runaway recombinational telomere elongation and rapid deletion in yeast. Mol. Cell. Biol. 25: 8064-8073.McEachern, M.J. and J.E. Haber. 2005. Telomerase-independent telomere maintenance in yeast. In: Telomeres, second edition. T. deLange, V. Lundblad, and E. Blackburn (eds). Cold Spring Harbor Laboratory Press. Groff-Vindman, C., S. Natarajan, A. Cesare, J.D. Griffith and M.J. McEachern. 2005. Recombination at dysfunctional long telomeres forms tiny double and single stranded t-circles. Mol. Biol. Cell 25: 4406-4412.Topcu, Z., K. Nickles, C. Davis and M.J. McEachern. 2005. Abrupt disruption of capping and a single source for recombinationally elongated telomeres in Kluyveromyces lactis. Proc Natl. Acad. Sci. USA 102: 3348-3353. Askree, S.H., T. Yehuda, S. Smolikov, R. Gurevich, J. Hawk, C. Coker, A. Krauskopf, M. Kupiec and M.J. McEachern. 2004. A genome-wide screen for Saccharomyces cerevisiae deletion mutants that affect telomere length. Proc Natl. Acad. Sci. USA 101: 8658-8663. Tomaska, L., M.J. McEachern and J. Nosek 2004. Alternatives to telomerase: Keeping linear chromosomes via telomeric circles. FEBS Lets. 567: 142-146. Nickles, K. and M.J. McEachern. 2004. Characterization of K. lactis Subtelomeric Sequences Including a Distal Element with Strong Purine/Pyrimidine Strand Bias. Yeast 21: 813-830. Underwood, D. H., C. Carroll and M.J. McEachern. 2004. Genetic dissection of the K. lactis telomere and evidence for telomere capping defects in TER1 mutants with long telomeres. Eukaryotic Cell 3:369-384. Underwood, D. H., R. Zinzen and M.J. McEachern. 2004. Template requirements for telomerase translocation in the yeast K. lactis. Mol. Cell Biol. 24: 912-923. Natarajan, S., C. Groff-Vindman and M.J. McEachern. 2003. Factors influencing the recombinational expansion and spread of telomeric tandem arrays in Kluyveromyces lactis. Eukaryotic Cell 2: 1115-1127. Natarajan, S. and M.J. McEachern. 2002. Recombinational telomere elongation promoted by DNA circles. Mol. Cell Biol. 22: 4512-4521. McEachern, M.J., D.H. Underwood and E.H. Blackburn. 2002. Dynamics of telomeric DNA turnover in yeast. Genetics 16: 63-73. Underwood, D.H. and M.J. McEachern. 2001. Totally mutant telomeres: singe-step mutagenesis of tandem repeat DNA sequences. BioTechniques 30: 934-938. McEachern, M.J. and S. Iyer. 2001. Short telomeres in yeast are highly recombinogenic. Molecular Cell 7: 695-704.\ McEachern, M.J., A. Krausfopf and E.H. Blackburn. 2000. Telomeres and their control. Annu. Rev. Genet. 34: 331-358. McEachern, M.J., S. Iyer, T.B. Fulton and E.H. Blackburn. 2000. Telomere fusions caused by mutating the terminal region of telomeric DNA. Proc. Natl. Acad. Sci. USA 97: 11409-11414. Cohn, M., M.J. McEachern and E.H. Blackburn. 1998. Telomeric sequence diversity within the genus Saccharomyces. Current Genetics 33: 83-91. McEachern, M.J. and E.H. Blackburn. 1997. Consequences of mutations that alter telomeres in the yeast K. lactis. Pp. 111-127 In: Pezcoller Foundation Symposia No. 8: Genomic Instability and Immortality in Cancer. E. Mihich and L. Hartwell (eds). Plenum Press, New York. Blackburn, E., A. Bhattacharyya, D. Gilley, K. Kirk, A. Krauskopf, M. McEachern, J. Prescott and T. Ware. 1997. The telomere and telomerase: how do they interact? Ciba Foundation Symposia 211: 2-13. McEachern, M.J. and E.H. Blackburn. 1996. Cap-prevented recombination between terminal telomeric repeat arrays (telomere CPR) maintains telomeres in K. lactis lacking telomerase. Genes and Dev. 10: 1822-1834. McEachern, M.J. and E.H. Blackburn. 1995. Runaway telomere elongation caused by telomerase RNA gene mutations. Nature 376: 403-409. McEachern, M.J. and E.H. Blackburn. 1994. A conserved motif within the exceptionally diverse telomeric sequences of budding yeasts. Proc. Natl. Acad. Sci. USA 91: 3453-3457. McEachern, M.J. and J.B. Hicks. 1993. Unusually large telomeric repeats in the yeast Candida albicans. Mol. Cell Biol. 13: 551-560.
