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Department of Molecular Medicine
 

Lee Sang Eun  Lee,  Ph.D.

Associate Professor/Leukemia and Lymphoma Society Scholar

Profile and Contact Information | Research | Laboratory

RESEARCH

 

Research Program

Cancer results from genetic and environmental insults leading to the accumulation of mutations in genes preventing the initiation and the progression of this disease. The ultimate cure of this disease will thus come from a better understanding of the mechanisms ensuring that damaged DNA is being repaired. DNA double strand break, where both strands of a DNA molecule in one chromosome break, is one of the most dangerous forms of DNA damage that can cause alterations of structure and expression of important genes (a.k.a. chromosome instability) as can be seen from many types of cancer. The importance of understanding DNA double-strand break repair process is further highlighted by the existence of several human diseases that lead to cancer predisposition. These diseases are the result of mutations in DNA double-strand break repair genes.

Our research program aims at elucidating DNA double-strand break repair mechanism in yeast model system using a combination of genetic and biochemical approaches. Specifically, we have initiated a genome wide screen for genes that are indispensable for the repair of chromosome breaks. Through this screen, we have identified several novel genes that affect the repair of chromosomal double-strand breaks. The current focus of our research is to delineate the functions of these gene products in repairing of DNA double-strand breaks and thus to illuminate the mechanistic insights into these processes. The results from our studies will constitute the foundation for studying the double-strand break repair pathway in human cells and are germane for dissecting the molecular basis for enhanced genetic instability in cancer patients.

 

Selected Publications

  1. Lee, S.E., Pellicioli, A., Demeter, J., Vaze, M., Gasch, A., Malkova, A. Botstein, D., Brown, P., Stearns, T., Foiani, M., and Haber, J.E. Arrest, adaptation and recovery following a chromosome double-strand break in Saccharomyces cerevisiae. Cold Spring Harbor Symposia on Quantitative Biology, Cold Spring Harbor Press. New York, LXV: 303-314, 2000.
  2. Pellicioli, A*., Lee. S.E.*, Foiana, M., and Haber, J.E. Regulation of Saccharomyces Rad53 checkpoint kinase during adaptation from G2/M arrest. Mol. Cell 7: 293-300, 2001 (*co first-author).
  3. Lee, S.E., Pellicioli, A., Malkova, A., Foiana, M., and Haber, J.E. The Saccharomyces recombination protein Tid1p is required for adaptation from G2/M arrest induced by a single double-strand break. Curr. Biol. 11: 1053-1057, 2001.
  4. Valencia, M., Bentele, M., Vaze, M.B., Hermann, G., Kraus, E., Lee, S.E., Schar, P., and Haber, J.E. NEJ1: a gene controlling nonhomologous end-joining in yeast. Nature 414: 666-669, 2001.
  5. Lee, S.E., Bressan, D.A., Petrini, J.H., and Haber, J.E. Complementation between N-terminal Saccharomyces cerevisiae mre11 alleles in DNA repair and telomere length maintenance. DNA Repair 1: 27-40, 2002.
  6. Vaze, M.B., Pellicioli, A., Ira, G., Lee, S.E., Liberi, G., Arbel-Eden, A., Foiani, M., and Haber, J.E. Recovery from checkpoint-mediated arrest after repair of a double-strand break requires Srs2 helicase. Mol. Cell. 10: 373-385, 2002.
  7. Leroy, C., Lee, S.E., Vaze, M.B., Ochsenbien, F., Guerois, R., Haber, J.E., and Marsolier-Kergoat, M.C. PP2C phosphatases Ptc2 and Ptc3 are required for DNA checkpoint inactivation after a double strand break. Mol. Cell. 11: 827-835, 2003.
  8. Lee, S.E., Pellicioli, A., Sugawara, N., Vaze, M., Foiani, M., and Haber, J.E. Yeast Rad52 and Rad51 recombination proteins define a second pathway of DNA damage assessment in response to a single double-strand break. Mol. Cell. Biol. 23: 8913-8923, 2003.
  9. Ma, J., Kim, E, Haber, J.E., and Lee, S.E. Yeast Mre11 and Rad1 proteins define a Ku-independent mechanism to repair double strand breaks lacking overlapping end sequences. Mol. Cell. Biol. 23: 8820-8828, 2003.
  10. Shim, E.Y., Ma, J-L., Oum, J-H., Yanez, Y., and Lee, S.E. The yeast chromatin remodeler RSC complex facilitates end joining repair of DNA double-strand breaks. Mol. Cell Biol. 25: 3934-3944, 2005.
  11. Shim, E.Y., Hong, S.J., Oum, J-H., Yanez, Y., Zhang, Y. and Lee, S.E. RSC mobilizes nucleosomes to improve accessibility of repair machinery to the damaged chromatin. Mol. Cell. Biol. 27: 1602-1613, 2007.
  12. Lee, K and Lee, S.E. Saccharomyces cerevisiae Sae2- and Tel1-dependent single strand DNA formation at DNA break promotes microhomology-mediated end joining. Genet. 176: 2003-2014, 2007.
  13. Zhang, Y., Hefferin, M.L., Chen, L., Shim, E.Y., Tseng, H.M., Kwon, Y., Sung, P., Lee, S.E. and Tomkinson, A.E. Role of Dnl4-Lif1 in nonhomologous end-joining repair complex assembly and suppression of homologous recombination. Nat. Struct. Mol. Biol. 14: 639-646, 2007.
  14. Li, F., Dong, J., Pan, P., Oum, J., Boeke, J.D. and Lee, S.E. Microarray-based genetic screen defines SAW1, a new gene required for Rad1/Rad10-dependent processing of recombination intermediates. Mol. Cell 30: 325-335, 2008.
  15. Lee, K., Zhang, Y. and Lee S.E. Saccharomyces cerevisiae ATM ortholog suppresses break-induced chromosome translocations. Nature 2008 (accepted).
  16. Banerjee, S., Smith, S., Oum, J.H., Liaw, H.-J., Hwang, J.-Y., Sikdar, N., Motegi, A., Lee, S.E. and Myung, K. Mph1, yeast FANCM orthologue directs proper repair and gross chromosomal rearrangement through its interaction with homologous recombination. J. Cell Biol. 2008 accepted.

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