Susan L. Smith

Susan L. Smith, PhD

Skirball Institute

Professor, Department of Pathology

Keywords
mechanisms of telomere function, telomere length regulation, sister chromatid cohesion, Tankyrase 1 and Poly(ADP-ribosyl)ation, cancer, genome integrity, metabolism, stem cell biology
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.

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These focus areas and their associated publications are derived from medical subject headings from PubMed.
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Professor, Department of Pathology

Advisor, Molecular Oncology and Immunology Graduate Program, Sackler

Coordinator, Molecular Pathogenesis Program, Skirball Institute

PhD from State University of New York at Stony Brook

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

Nucleic acids research. 2016 Jul 27; 44(13):6363-6376

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

Diabetologia. 2016 Mar; 59(3):582-591

Ramamoorthy, Mahesh; Smith, Susan

Cancer cell. 2015 Sep 14; 28(3):357-369

Single-Molecule Imaging Reveals Dynamics of SA1-TRF1 Interactions on Telomeric DNA [Meeting Abstract]

Lin, Jiangguo; Chen, Haijiang; Kaur, Parminder; Miao, Wang; Countryman, Preston; You, Changjiang; Piehler, Jacob; Tao, Yizhi J; Smith, Susan; Wang, Hong

Biophysical journal. 2015 JAN 27; 108(2):206A-206A

Kim, Mi Kyung; Smith, Susan

Molecular biology of the cell. 2014 Jan; 25(1):30-40

Bisht, Kamlesh K; Daniloski, Zharko; Smith, Susan

Journal of cell science. 2013 Aug 01; 126(Pt 15):3493-3503

Bisht, Kamlesh K; Dudognon, Charles; Chang, William G; Sokol, Ethan S; Ramirez, Alejandro; Smith, Susan

Molecular & cellular biology. 2012 Aug; 32(15):3044-3053