Susan L Smith

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Susan Smith

Professor, Department of Pathology
Grad Ad Molecular Onc & Imm Grad Pgm

Contact Info

Address
540-562 First Avenue
New York, NY 10016

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


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

Functional interplay between SA1 and TRF1 in telomeric DNA binding and DNA-DNA pairing
Lin, Jiangguo; Countryman, Preston; Chen, Haijiang; Pan, Hai; Fan, Yanlin; Jiang, Yunyun; Kaur, Parminder; Miao, Wang; Gurgel, Gisele; You, Changjiang; Piehler, Jacob; Kad, Neil M; Riehn, Robert; Opresko, Patricia L; Smith, Susan; Tao, Yizhi Jane; Wang, Hong. Functional interplay between SA1 and TRF1 in telomeric DNA binding and DNA-DNA pairing. Nucleic acids research. 2016 Jun 13;:?-? (2145082)

Single-Molecule Imaging Reveals Dynamics of SA1-TRF1 Interactions on Telomeric DNA
Lin, Jiangguo; Chen, Haijiang; Kaur, Parminder; Miao, Wang; Countryman, Preston; You, Changjiang; Piehler, Jacob; Tao, Yizhi J; Smith, Susan; Wang, Hong. Single-Molecule Imaging Reveals Dynamics of SA1-TRF1 Interactions on Telomeric DNA [Meeting Abstract]. Biophysical journal. 2015 JAN 27;108(2):206A-206A (1821952)

Loss of ATRX Suppresses Resolution of Telomere Cohesion to Control Recombination in ALT Cancer Cells
Ramamoorthy, Mahesh; Smith, Susan. Loss of ATRX Suppresses Resolution of Telomere Cohesion to Control Recombination in ALT Cancer Cells. Cancer cell. 2015 Sep 14;28(3):357-369 (1778202)

The PARsylation activity of tankyrase in adipose tissue modulates systemic glucose metabolism in mice
Zhong, Linlin; Ding, Yun; Bandyopadhyay, Gautam; Waaler, Jo; Borgeson, Emma; Smith, Susan; Zhang, Mingchen; Phillips, Susan A; Mahooti, Sepi; Mahata, Sushil K; Shao, Jianhua; Krauss, Stefan; Chi, Nai-Wen. The PARsylation activity of tankyrase in adipose tissue modulates systemic glucose metabolism in mice. Diabetologia. 2015 Dec 2;59(3):582-591 (1863522)

SA1 binds directly to DNA through its unique AT-hook to promote sister chromatid cohesion at telomeres
Bisht, Kamlesh K; Daniloski, Zharko; Smith, Susan. SA1 binds directly to DNA through its unique AT-hook to promote sister chromatid cohesion at telomeres. Journal of cell science. 2013 May 31;126(Pt 15):3493-3503 (484052)