The University of Chicago BA 12/75 Biology
The University of Chicago PhD 06/81 Biochemistry
The University of Chicago Post Doc 1981-1985 Molecular Genetics
California Institute of Technology Res. Fellow 1985-1987 Biochemistry
Positions and Employment
1987-1996 Assistant Member, Program in Molecular Biology, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center
1987-1996 Assistant Professor, Sloan-Kettering Institute Division, Graduate School of Medical Sciences, Cornell University
1996-1997 Associate Professor, Department of Biochemistry, Tulane University Medical School, Tulane University HSC
1998-2005 Associate Professor (tenured), Department of Biochemistry, Tulane University Medical School, Tulane University HSC
2005-Present Professor, Department of Biochemistry, School of Medicine, Tulane University HSC
2005-2006 Visiting Professor, Department of Molecular Biology and Cell Biology, Northwestern University
2012-2013 Chair, Departmental Faculty Search Committee Adjunct Faculty
2002-Present Adjunct Faculty, Department of Human Genetics
2009-Present Member, Tulane Aging Center
Role of telomere dynamics in chromosome stability and transcriptional regulation
The integrity of the telomere nucleoprotein structures at the end of eukaryotic chromosomes is essential for genomic stability. Telomeric structures must both accommodate the end-replication problem and serve as a buffer against promiscuous nuclease and recombination activities. While most eukaryotes utilize the ribonucleoprotein telomerase for the addition of simple sequence repeats, alternative recombination-based pathways (ALT) exist in both yeast and vertebrates. In humans, ALT pathways are responsible for immortality in 15% of tumors. Our long-term goal is to increase our knowledge of the mechanism, efficiency, and regulation of telomere/telomere recombination that will ultimately provide the means for its manipulationThis information will be critical for the control of the ALT pathway of telomere addition in humans.
Our laboratory has investigated the structure and replication of telomeres using yeast Saccharomyces cerevisiae as a genetic model system. Telomeres are the structures present at the termini of eukaryotic chromosomes composed of G+T-rich DNA and a plethora of proteins that allow complete replication of the telomere and protection against factors that can act to degrade chromosomes. We have been exploring several novel aspects of telomere function. Multiple studies have implicated defects in telomeres and the onset of oncogenesis and chromosomal catastrophe. While most eukaryotic telomeres are replicated by the reverse transcriptase telomerase, we have focused on the second recombinational mode of telomere addition and deletion, both of which are highly maintained in vertebrates. Some protein complexes involved in this recombination pathway are present exclusively at the telomere while others are present both in replication and DNA repair. Using alleles of mutations in gene that encode components of these complexes, we have investigated the mechanism of telomere recombination. These studies have led to the discovery that telomeres have an epigenetic and heritable component. These latter finding provides a completely novel view of telomere regulation in yeast and in vertebrate oncogenesis.
Dynamics of yeast telomeres as related to sesescence
Levens, D., Lustig, A.J., and Rabinowitz, M. 1981. Purification of mitochondrial RNA polymerase from Saccharomyces cerevisiae. J. Biol. Chem. 256:1474-1481.
Lustig, A., J., Padmanaban, G., and Rabinowitz, M. 1982. Regulation of the nuclear-coded peptides of cytochrome c oxidase. Biochemistry 21:309-316.
Lustig, A.J., Levens, D. and Rabinowitz, M. 1982. The biogenesis and regulation of yeast mitochondrial RNA polymerase. J. Biol. Chem. 257:5800-5808.
Lustig, A.J. and Petes, T.D. 1984. Long polyA tracts in the human genome are associated with the Alu family of repeated elements. J. Mol. Biol. 180:753-759.
Lustig, A.J. and Petes, T.D. 1986. Identification of yeast mutants with altered telomere structure. Proc. Natl. Acad. Sci. 83:1398-1402.
Lustig, A.J., Lin, R. -J., and Abelson, J. 1986. The yeast RNA gene products are essential for mRNA splicing in vitro. Cell 47:953-963.
Lin, R.-J., Lustig, A.J., and Abelson, J. 1987. Splicing of yeast nuclear pre-mRNA in vitro requires a functional 40S spliceosome and several extrinsic factors. Genes Dev. 1:7-18.
Chang, T -S., Clark, M.W., Lustig, A.J., Cusick, M.E., and Abelson, J. 1988. The RNA11 protein is associated with the yeast spliceosome and is localized in the periphery of the cell nucleus. Mol. Cell. Biol. 8:2379-2393.
Lustig, A.J., Kurtz, S., and Shore, D. 1990. Involvement of the silencer and UAS binding protein RAP1 in regulation of telomere length. Science 250:549-553.
Lustig, A.J. 1992. Hoogsteen G-G base pairing is dispensable for telomere healing in yeast. Nucleic Acids Res. 20:3021-3028.
Kyrion, G., Boakye, K.A., and Lustig, A.J. 1992. C-terminal truncation of RAP1 results in the deregulation of telomere size, stability and function in Saccharomyces cerevisiae. Mol. Cell. Biol. 12:5159-5173.
Kyrion, G., Liu, K., Liu, C., and Lustig, A.J. 1993. RAP1 and telomere structure regulate telomere position effects in Saccharomyces cerevisiae. Genes Dev. 7:1146-1159.
Liu, C., Mao, X., and Lustig, A.J. 1994. Mutational analysis defines a C-terminal tail domain of RAP1 essential for telomeric silencing in Saccharomyces cerevisiae. Genetics 118:1025-1040.
Cockell, M. Palladino, F., Laroche, T., Kyrion, G., Liu, C., Lustig, A. J, and Gasser, S. 1995. The Carboxy-termini of SIR4 and RAP1 affect SIR3 localization: Evidence for a multicomponent complex required for telomeric silencing. J. Cell. Biol. 129:909-924.
Liu, C. and Lustig, A. J. 1996. Genetic analysis of Rap1p/Sir3p interactions in telomeric and HML silencing in Saccharomyces cerevisiae. Genetics 143:81-93.
Lustig, A.J., Liu, C., Zhang, C., and Hanish, J. P. 1996. Tethered Sir3p nucleates silencing at telomeres and internal loci in Saccharomyces cerevisiae. Mol. Cell. Biol. 16:2483-2495.
Li, B. and Lustig, A. J. 1996. A novel mechanism for telomere size control in Saccharomyces cerevisiae. Genes Dev. 10:1310-1326.
Lustig, A.J. 1997. The identification of telomerase subunits: catalyzing telomere research. Trends Cell. Biol. 7:299-302.
Polotnianka, R.M., Liu, J. and Lustig, A.J. 1998. The yeast Ku heterodimer is essential for protection against nucleolytic and recombinational activities. Current Biology 8:831-834.
Park, Y., Hanish, J.. and Lustig, A.J. 1998. Sir3p domains involved in the nucleation of telomeric silencing in Saccharomyces cerevisiae. Genetics 150:977-986.
Lustig, A.J. 1998. Mechanisms of silencing in Saccharomyces cerevisiae. Curr. Opin. Genet. Dev. 8:233-239.
Lustig, A.J. 1998. Telomerases and non-LTR Retrotransposons: Different Means to a Common End? Current Biology 8:R161-R164.
Lustig, A.J. 1999. Crisis intervention: The role of telomerase. Proc. Natl. Acad. Sci. U.S.A. 96:3339-3341.
Lustig, A.J. 1999. The kudos of non-homologous end joining. Nat. Genet. 23:130-131.
Park, Y. and Lustig, A.J. 2000. Telomere structure regulates the heritability of repressed subtelomeric chromatin in Saccharomyces cerevisiae. Genetics 154:587-598.
Bucholc, M., Park, Y., and Lustig, A. J. 2001. Intrachromatid excision of telomeric DNA as a mechanism for telomere size control in S. cerevisiae. Mol. Cell. Biol. 21:6559-6573.
Lustig, A.J. 2001. Cdc13 subcomplexes regulate multiple telomere functions. Nat. Struct. Biol. 8:297-300.
Williams, B. and Lustig, A. J. 2003. The paradoxical relationship between NHEJ and telomere fusion. Mol. Cell 11:1125-1126.
Wyatt, H., Liaw, H., Green, G. R., and Lustig, A.J. 2003 Multiple role for Saccharomyces cerevisiae histone H2A in telomere position effect, spt suppression and DSB Repair. Genetics 164:47-64.
Lustig, A.J. 2003. Opinion: Does telomere rapid deletion in yeast hold clues to catastrophic telomere loss in mammals? Nature Reviews Genetics 4:916-923 (perspective; peer-reviewed).
Lustig, A.J. 2004. Telomerase RNA: A Flexible RNA Scaffold for Telomerase Biosynthesis. Current Biology 14:R565-567.
Joseph, I. Jia, D., and Lustig, A. J. 2005. Ndj1-dependent telomere size resetting in yeast meiosis, Current Biology 15:231-237.
Williams B., Bhattacharyya M.K., Lustig A.J. 2005. Mre11p Nuclease Activity is Dispensable for Telomeric Rapid Deletion. DNA Repair 4:994-1005.
Bhattacharyya, M. and Lustig, A.J. 2006. Telomere dynamics in genome stability. TIBS 31:112-12.
Liaw, H. and Lustig, A.J. 2006 The Sir3 C-Terminal Domain Contributes to the Initiation and Spreading of Heterochromatin. MCB 26:7616-7631.
Joseph, I. and Lustig, A. J. 2007. “Telomeres in meiotic recombination: The yeast side story”. CMLS 64:125-130.
Bhattacharyya, M.K, Kametra, K.M, and Lustig, A. J. 2008. Multiple Domains for Mre11 Monitoring of Telomere Damage. Chromosoma 117: 357-366.
Lustig, A. 2009. Separating Effects of Telomere Size from the Mechanism of Elongation. EMBO J. (invited) 28:793-794.
Joseph, I., Kumari, A., Bhattacharyya, M.K, Gao, H., Li, B., and Lustig, A. J. 2010. An mre11 Mutation that Promotes Telomere Recombination and an Efficient Bypass of Senescence. Genetics 185:761-770.
Liu, A., Qi,Y., Ge, Y., Duplessis, T., Rowan, B.G., Ip, C., Cheng, H., Rennie, P.S., Horikawa, I., Lustig, A.J., Yu, Q., Zhang, H., and Dong, Y. 2010. Telomerase as an important target of androgen-signaling blockade for prostate cancer treatment. Molecular Cancer Therapeutics 9: 2016-224 (paper highlighted in journal).
Lustig, A.J. and Sgura, A. 2013. A New Era of Allele-Specific Diagnostics?. Frontiers in Genetics 07/2013; 4(134):1., DOI:10.3389/fgene.2013.00134.
Gao, H., Moss, D.L., Parke, C., Tatum, D., and Lustig, A.J. 2014. The Ctf18RFC Clamp Loader Is Essential for Telomere Stability in Telomerase-Negative and mre11 Mutant Alleles. PLoS ONE 02/2014; 9(2):e88633., DOI:10.1371/journal.pone.0088633.
Lustig, A.J. 2015. Potential Risks in the Paradigm of Basic to Translational Research: A Critical Evaluation of qPCR Telomere Size Techniques. J Cancer Epidemiol Treat. 09/2015; 1(1)., DOI:10.24218/jcet.2015.08.
Lustig, A.J. 2016. Hypothesis: Paralog Formation from Progenitor Proteins and Paralog Mutagenesis Spur the Rapid Evolution of Telomere Binding Proteins. Frontiers in Genetics 02/2016; Front. Genet.,(10 February2016)., DOI:10.3389/fgene.2016.00010.
Runge, K.W. and Lustig, A.J. (Editorial) 2016. The Evolving Telomere. Frontiers in Genetics 04/2016; 7., DOI:10.3389/fgene.2016.00050.
Baek, I., Moss, D., and Lustig, A.J. 2017. Mre11 Regulated Conservative Segregation of Chromatin and Heritability in Telosomes of Saccharomyces cerevisiae, PLOS One, 09/2017 doi: 10.1371/journal.pone.0183549.
Lustig, A.J., Goebl, M., and Petes, T.D. 1986. Structure and genetic analysis of the yeast genome. In: UCLA Symposia on Molecular and Cellular Biology, New Series, Vol. 33 (J. Hicks, ed), Alan R. Liss, New York, pp. 251-269.
Lustig, A.J., Lin, R. -J., and Abelson, J. 1987. mRNA splicing in yeast. In: New Perspectives on the Molecular Biology of RNA (B. Dudock, M. Inoye, eds.), Academic Press, New York, pp. 113-131.
Lustig, A.J. and Petes, T.D. 1993. The genetic control of simple sequence stability in yeast. Genome Analysis 7: 79-106 [invited review].
Lustig, A.J. 1996. Methods in the analysis of telomere function in Saccharomyces cerevisiae. Microbial Genome Methods (K. Adolph, ed.), CRC Press, Boca Raton, Florida, pp. 37-60 [invited review].