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Biosketch / Results /

Susan L Smith, Ph.D.

Professor; Grad Ad Molecular Onc & Imm Grad Pgm
Department of Pathology (Skirball) [1] and Molecular Pathogenesis

Contact Info

Address
540 First Avenue
Floor 2 Room Lab 9
Skirball Institute
New York, NY 10016-6481

212-263-2540
Susan.Smith@med.nyu.edu


[3]

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Education

— Rockefeller University, PostDoctoral Training
— State University of New York at Stony Brook, Graduate Education

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Research Summary

Faithful duplication and segregation of DNA are essential for the continuity of life. Errors in chromosome replication and segregation can lead to aneuploidy, which can have serious consequences for human growth and development, and drive cancer in somatic cells. Telomeres, the ends of eukaryotic chromosomes, require special mechanisms for their protection, replication, and cohesion. We study human telomeres and the mechanisms that control their function in normal cells, stem cells, and in cancer. Human telomere function is regulated by the dedicated six-subunit telomere-binding complex shelterin and by a number of other shelterin-binding factors, such as the poly(ADP-ribose) polymerase tankyrase 1, that associate transiently with telomeres. The goal of our research is to understand how shelterin and its accessory factors regulate telomere structure and function, and control access to telomerase, the reverse transcriptase that adds telomere repeats to chromosome ends. We have several areas of focus in the lab: 1) the regulation of shelterin stability and function by post-translational modification, including poly(ADP-ribosyl)ation, and ubiquitylation and proteasomal degradation; 2) the mechanisms that control the establishment of sister chromatid cohesion at telomeres during DNA replication and the resolution of sister chromatid cohesion at telomeres in mitosis; 3) the role of defective telomere cohesion in the human stem cell disease dyskeratosis congenita; and 4) the cell cycle regulation and non-telomeric functions of tankyrase 1, including its role at spindle poles and centrosomes. Our long-term goal is to understand the mechanisms that ensure genome integrity and cell survival.

Research Interests

Mechanisms of Telomere Function, Telomere length Regulation, Sister Chromatid Cohesion, Tankyrase 1 and Poly(ADP-ribosyl)ation

Research Keywords

Telomeres, Shelterin, Tankyrase, Telomerase, Sister Chromatid Cohesion

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All data from NYU Health Sciences Library Faculty Bibliography — -

Contact:
http://hsl.med.nyu.edu/faculty-bibliography-search [8]

TIN2 stability is regulated by the E3 ligase Siah2
Bhanot, Monica; Smith, Susan
2012 Jan;32(2):376-384, Molecular & cellular biology
— id: 157613, year: 2012, vol: 32, page: 376, stat: Journal Article,

GDP-Mannose-4,6-Dehydratase Is a Cytosolic Partner of Tankyrase 1 That Inhibits Its Poly(ADP-Ribose) Polymerase Activity
Bisht, Kamlesh K; Dudognon, Charles; Chang, William G; Sokol, Ethan S; Ramirez, Alejandro; Smith, Susan
2012 Aug;32(15):3044-3053, Molecular & cellular biology
— id: 173024, year: 2012, vol: 32, page: 3044, stat: Journal Article,

A role for sister telomere cohesion in telomere elongation by telomerase
Houghtaling, Benjamin R; Canudas, Silvia; Smith, Susan
2012 Jan 1;11(1):19-25, Cell cycle
— id: 149956, year: 2012, vol: 11, page: 19, stat: Journal Article,

Tankyrase 1 regulates centrosome function by controlling CPAP stability
Kim, Mi Kyung; Dudognon, Charles; Smith, Susan
2012 Aug;13(8):724-732, EMBO reports
— id: 174386, year: 2012, vol: 13, page: 724, stat: Journal Article,

mRNA Decay Factor AUF1 Maintains Normal Aging, Telomere Maintenance, and Suppression of Senescence by Activation of Telomerase Transcription
Pont, Adam R; Sadri, Navid; Hsiao, Susan J; Smith, Susan; Schneider, Robert J
2012 Jul;47(1):5-15, Molecular cell
— id: 173022, year: 2012, vol: 47, page: 5, stat: Journal Article,

Poly(ADP-ribose) polymerase 3 (PARP3), a newcomer in cellular response to DNA damage and mitotic progression
Boehler, Christian; Gauthier, Laurent R; Mortusewicz, Oliver; Biard, Denis S; Saliou, Jean-Michel; Bresson, Anne; Sanglier-Cianferani, Sarah; Smith, Susan; Schreiber, Valerie; Boussin, Francois; Dantzer, Francoise
2011 Feb 15;108(7):2783-2788, Proceedings of the National Academy of Sciences of the United States of America
— id: 134153, year: 2011, vol: 108, page: 2783, stat: Journal Article,

A role for heterochromatin protein 1{gamma} at human telomeres
Canudas, Silvia; Houghtaling, Benjamin R; Bhanot, Monica; Sasa, Ghadir; Savage, Sharon A; Bertuch, Alison A; Smith, Susan
2011 Sep 1;25(17):1807-1819, Genes & development
— id: 137073, year: 2011, vol: 25, page: 1807, stat: Journal Article,

Differential regulation of telomere and centromere cohesion by the Scc3 homologues SA1 and SA2, respectively, in human cells
Canudas, Silvia; Smith, Susan
2009 Oct 19;187(2):165-173, Journal of cell biology
— id: 104723, year: 2009, vol: 187, page: 165, stat: Journal Article,

Sister telomeres rendered dysfunctional by persistent cohesion are fused by NHEJ
Hsiao, Susan J; Smith, Susan
2009 Feb 23;184(4):515-526, Journal of cell biology
— id: 93576, year: 2009, vol: 184, page: 515, stat: Journal Article,

The long and short of it: a new isoform of TIN2 in the nuclear matrix
Smith, Susan
2009 Mar 15;8(6):797-798, Cell cycle
— id: 137817, year: 2009, vol: 8, page: 797, stat: Journal Article,

The SAGA continues...to the end
Smith, Susan
2009 Aug 14;35(3):256-258, Molecular cell
— id: 101646, year: 2009, vol: 35, page: 256, stat: Journal Article,

Tankyrase 1 and tankyrase 2 are essential but redundant for mouse embryonic development
Chiang, Y Jeffrey; Hsiao, Susan J; Yver, Dena; Cushman, Samuel W; Tessarollo, Lino; Smith, Susan; Hodes, Richard J
2008 ;3(7):e2639-e2639, PLoS ONE
— id: 88580, year: 2008, vol: 3, page: e2639, stat: Journal Article,

Tankyrase function at telomeres, spindle poles, and beyond
Hsiao, Susan J; Smith, Susan
2008 Jan;90(1):83-92, Biochimie
— id: 76329, year: 2008, vol: 90, page: 83, stat: Journal Article,

Protein requirements for sister telomere association in human cells
Canudas, Silvia; Houghtaling, Benjamin R; Kim, Ju Youn; Dynek, Jasmin N; Chang, William G; Smith, Susan
2007 Nov 28;26(23):4867-4878, EMBO journal
— id: 75398, year: 2007, vol: 26, page: 4867, stat: Journal Article,

Tankyrase 2 poly(ADP-ribose) polymerase domain-deleted mice exhibit growth defects but have normal telomere length and capping
Hsiao, Susan J; Poitras, Marc F; Cook, Brandoch D; Liu, Yie; Smith, Susan
2006 Mar;26(6):2044-2054, Molecular & cellular biology
— id: 64582, year: 2006, vol: 26, page: 2044, stat: Journal Article,

NuMA is a major acceptor of poly(ADP-ribosyl)ation by tankyrase 1 in mitosis
Chang, William; Dynek, Jasmin N; Smith, Susan
2005 Oct 15;391(2):177-184, Biochemical journal
— id: 58149, year: 2005, vol: 391, page: 177, stat: Journal Article,

Resolution of sister telomere association is required for progression through mitosis
Dynek, Jasmin N; Smith, Susan
2004 Apr 2;304(5667):97-100, Science
— id: 42576, year: 2004, vol: 304, page: 97, stat: Journal Article,

A dynamic molecular link between the telomere length regulator TRF1 and the chromosome end protector TRF2
Houghtaling, Benjamin R; Cuttonaro, Leanora; Chang, William; Smith, Susan
2004 Oct 21;14(18):1621-1631, Current biology. CB
— id: 46295, year: 2004, vol: 14, page: 1621, stat: Journal Article,

Functional subdomain in the ankyrin domain of tankyrase 1 required for poly(ADP-ribosyl)ation of TRF1 and telomere elongation
Seimiya, Hiroyuki; Muramatsu, Yukiko; Smith, Susan; Tsuruo, Takashi
2004 Mar;24(5):1944-1955, Molecular & cellular biology
— id: 137818, year: 2004, vol: 24, page: 1944, stat: Journal Article,

TRF1 is degraded by ubiquitin-mediated proteolysis after release from telomeres
Chang, William; Dynek, Jasmin N; Smith, Susan
2003 Jun 1;17(11):1328-1333, Genes & development
— id: 36833, year: 2003, vol: 17, page: 1328, stat: Journal Article,

Role for the Related Poly(ADP-Ribose) Polymerases Tankyrase 1 and 2 at Human Telomeres
Cook, Brandoch D; Dynek, Jasmin N; Chang, William; Shostak, Grigoriy; Smith, Susan
2002 Jan 1;22(1):332-342, Molecular & cellular biology
— id: 24853, year: 2002, vol: 22, page: 332, stat: Journal Article,

The telomeric poly(ADP-ribose) polymerase, tankyrase 1, contains multiple binding sites for telomeric repeat binding factor 1 (TRF1) and a novel acceptor, 182-kDa tankyrase-binding protein (TAB182)
Seimiya, Hiroyuki; Smith, Susan
2002 Apr 19;277(16):14116-14126, Journal of biological chemistry