Professor/Leukemia and Lymphoma Society Scholar
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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.
- Li F, Dong J, Eichmiller R, Holland C, Minca E, Prakash R, Sung P, Shim EY, Surtees JA, and Lee SE: (2013) Role of Saw1 in Rad1/Rad10 complex assembly at recombination intermediates in budding yeast. EMBO J. 32(3): 461-72.
- Villarreal DD, Lee K, Deem A, Shim EY, Malkova A, and Lee SE: (2012) Microhomology directs diverse DNA break repair pathways and chromosomal translocations. PLoS Genet. 8(11): e1003026.
- Oum JH, Seong C, Kwon Y, Ji JH, Sid A, Ramakrishnan S, Ira G, Malkova A, Sung P, Lee SE, and Shim EY: (2011) RSC facilitates Rad59-dependent homologous recombination between sister chromatids by promoting cohesin loading at DNA double-strand breaks. Mol Cell Biol. 31(19): 3924-37.
- Chen X, Niu H, Chung WH, Zhu Z, Papusha A, Shim EY, Lee SE, Sung P, and Ira G: (2011) Cell cycle regulation of DNA double-strand break end resection by Cdk1-dependent Dna2 phosphorylation. Nat Struct Mol Biol. 18(9): 1015-9.
- Nicolette ML, Lee K, Guo Z, Rani M, Chow JM, Lee SE, and Paull TT: (2010) Mre11-Rad50-Xrs2 and Sae2 promote 5' strand resection of DNA double-strand breaks. Nat Struct Mol Biol. 17(12): 1478-85.
- Shim EY, Chung WH, Nicolette ML, Zhang Y, Davis M, Zhu Z, Paull TT, Ira G, and Lee SE: (2010) Saccharomyces cerevisiae Mre11/Rad50/Xrs2 and Ku proteins regulate association of Exo1 and Dna2 with DNA breaks. EMBO J. 29(19): 3370-80.
- Toh GW, Sugawara N, Dong J, Toth R, Lee SE, Haber JE, and Rouse J: (2010) Mec1/Tel1-dependent phoshorylation of SIx4 stimulates Rad1-Rad10-dependent cleavage of non-homologous DNA tails. DNA Repair (Amst). 9(6): 718-26.
- Zhang Y, Shim EY, Davis M, and Lee SE: (2009) Regulation of repair choice: Cdk1 suppresses recruitment of end joining factors at DNA breaks. DNA Repair (Amst). 8(10): 1235-41.
- Lee SE and Myung KJ: (2009) Faithful after break-up: suppression of chromosome translocations. Cell Mol Life Sci. 66(19): 3149-60.
- McVey M and Lee SE: (2008) MMEJ repair of double-strand breaks (director's cut): deleted sequences and alternative endings. Trends Genet. 24(11): 529-38.
- Zhu Z, Chung WH, Shim EY, Lee SE, and Ira G: (2008) Sgs1 helicase and two nucleases Dna2 and Exo1 resect DNA double-strand break ends. Cell. 134(6): 981-94.
- Lee K, Zhang Y, and Lee SE: (2008) Saccharomyces cerevisiae ATM orthologue suppresses break-induced chromosome translocations. Nature. 454(7203): 543-6.
- Banerjee S, Smith S, Oum JH, Liaw HJ, Hwang JY, Sikdar N, Motegi A, Lee SE, and Myung K: (2008) Mph1p promotes gross chromosomal rearrangement through partial inhibition of homologous recombination. J Cell Biol. 181(7): 1083-93.
- Li F, Dong J, Pan X, Oum JH, Boeke JD, and Lee SE: (2008) Microarray-based genetic screen defines SAW1, a new gene required for Rad1/Rad10-dependent processing of recombination intermediates. Mol Cell. 30(3): 325-35.
- Zhang Y, Hefferin ML, Chen L, Shim EY, Tseng HM, Kwon Y, Sung P, Lee SE, and Tomkinson AE: (2007) Role of Dnl4-Lif1 in nonhomologous end-joining repair complex assembly and suppression of homologous recombination. Nat Struct Mol Biol. 14(7): 639-46.
- Lee K and Lee SE: (2007) Saccharomyces cerevisiae Sae2- and Tel1-dependent single-strand DNA formation at DNA break promotes microhomology-mediated end joining. Genetics. 176(4): 2003-14.
- Shim EY, Hong SJ, Oum JH, Yanez Y, Zhang Y, and Lee SE: (2007) RSC mobilizes nucleosomes to improve accessibility of repair machinery to the damaged chromatin. Mol Cell Biol. 27(5): 1602-13.
- Shim EY, Ma JL, Oum JH, Yanez Y, and Lee SE: (2005) The yeast chromatin remodeler RSC complex facilitates end joining repair of DNA double-strand breaks. Mol Cell Biol. 25(10): 3934-44.
- Ma JL, Kim EM, Haber JE, and Lee SE: (2003) Yeast Mre11 and Rad1 proteins define a Ku-independent mechanism to repair double-strand breaks lacking overlapping end sequences. Mol Cell Biol. 23(23): 8820-8.
- Lee SE, Pellicioli A, Vaze MB, Sugawara N, Malkova A, Foiani M, and Haber JE: (2003) 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(23): 8913-23.
- Leroy C, Lee SE, Vaze MB, Ochsenbien F, Guerois R, Haber JE, and Marsolier-Kergoat MC: (2003) PP2C phosphatases Ptc2 and Ptc3 are required for DNA checkpoint inactivation after a double-strand break. Mol Cell. 11(3): 827-35.
- Vaze MB, Pellicioli A, Lee SE, Ira G, Liberi G, Arbel-Eden A, Foiani M, and Haber JE: (2002) Recovery from checkpoint-mediated arrest after repair of a double-strand break requires Srs2 helicase. Mol Cell. 10(2): 373-85.
- Lee SE, Bressan DA, Petrini JH, and Haber JE: (2002) Complementation between N-terminal Saccharomyces cerevisiae mre11 alleles in DNA repair and telomere length maintenance. DNA Repair (Amst). 1(1): 27-40.
- Valencia M, Bentele M, Vaze MB, Hermann G, Kraus E, Lee SE, Schar P, and Haber JE: (2001) NEJ1 controls non-homologous end joining in Saccharomyces cerevisiae. Nature. 414(6864): 666-9.
- Lee SE, Pellicioli A, Malkova A, Foiana M, and Haber JE: (2001) The Saccharomyces recombination protein Tid1p is required for adaptation from G2/M arrest induced by a single double-strand break. Curr Biol. 11(13): 1053-7
- Pellicioli A*, Lee SE*, Lucca C, Foiana M, and Haber JE: (2001) Regulation of Saccharomyces Rad53 checkpoint kinase during adaptation from DNA damage-induced G2/M arrest. Mol Cell. 7(2): 293-300. (*co first-author).
- Lee SE, Pellicioli A, Demeter J, Vaze MP, Gasch AP, Malkova A, Brown PO, Botstein D, Stearns T, Foiani M, and Haber JE: (2000) Arrest, adaptation and recovery following a chromosome double-strand break in Saccharomyces cerevisiae. Cold Spring Harb Symp Quant Biol., Cold Spring Harbor Press. New York, 65: 303-14.