Susan L Smith

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Susan Smith

Professor, Department of Pathology
Skirball Institute

Contact Info

540-562 First Avenue
New York, NY 10016



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

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

Persistent telomere cohesion triggers a prolonged anaphase
Kim, Mi Kyung; Smith, Susan
2014-02-03; 1059-1524,Molecular biology of the cell - id: 781822, year: 2014 Journal Article

SA1 binds directly to DNA through its unique AT-hook to promote sister chromatid cohesion at telomeres
Bisht, Kamlesh K; Daniloski, Zharko; Smith, Susan
2013-08-12; 0021-9533,Journal of cell science - id: 484052, year: 2013 Journal Article

TIN2 stability is regulated by the E3 ligase Siah2
Bhanot, Monica; Smith, Susan
2012-03-01; 0270-7306,Molecular & cellular biology - id: 157613, year: 2012 Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.

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
2012-07-24; 0270-7306,Molecular & cellular biology - id: 173024, year: 2012 Journal Article

A role for sister telomere cohesion in telomere elongation by telomerase
Houghtaling, Benjamin R; Canudas, Silvia; Smith, Susan
2012-02-05; 1551-4005,Cell cycle - id: 149956, year: 2012