Professor, “The Recruitment Program of Global Experts”
Chromosome is the major carrier of genetic information. The alteration of chromosomal structure determines the gene expression profile and cell fate. Telomere is the very ends of eukaryotic chromosomes. It is of importance for telomere and telomerase to maintain the integrity of genomes and the stability of chromosomes. Large amount of proteins and protein complexes are involved in epigenetics, which play essential roles in controlling many cellular events. Dys-regulation of chromatin structure and stability caused by abnormalities on DNA damage repair accounts for many human diseases. Studies of the proteins and protein complexes related to these diseases will provide foundations for developing novel diagnostic and therapeutic approaches. In our lab, we focus on three major research areas: (1) Telomere, telomerase and chromosomal stability; (2) Structural and functional studies of the proteins and protein complexes in epigenetics; (3) SOSS complex and DNA damage repair.
1. Yu, E.Y., Sun, J., Lei, M. and Lue, N.F. (2012) Analyses of Candida Cdc13 orthologues revealed a novel OB fold dimer arrangement, dimerization-assisted DNA binding, and substantial structural differences between Cdc13 and RPA70. Mol Cell Biol, 32, 186-198.
2. Huang, J., Gurung, B., Wan, B., Matkar, S., Veniaminova, N.A., Wan, K., Merchant, J.L., Hua, X. and Lei, M. (2012) The same pocket in menin binds both MLL and JUND but has opposite effects on transcription. Nature, 482, 542-546.
3. Chen, Y., Cao, F., Wan, B., Dou, Y. and Lei, M. (2012) Structure of the SPRY domain of human Ash2L and its interactions with RbBP5 and DPY30. Cell Res.
4. Zeng, Z., Min, B., Huang, J., Hong, K., Yang, Y., Collins, K. and Lei, M. (2011) Structural basis for Tetrahymena telomerase processivity factor Teb1 binding to single-stranded telomeric-repeat DNA. Proc Natl Acad Sci U S A, 108, 20357-20361.
5. Sun, J., Yang, Y., Wan, K., Mao, N., Yu, T.Y., Lin, Y.C., DeZwaan, D.C., Freeman, B.C., Lin, J.J., Lue, N.F. and Lei, M. (2011) Structural bases of dimerization of yeast telomere protein Cdc13 and its interaction with the catalytic subunit of DNA polymerase alpha. Cell Res, 21, 258-274.
6. Chen, Y., Wan, B., Wang, K.C., Cao, F., Yang, Y., Protacio, A., Dou, Y., Chang, H.Y. and Lei, M. (2011) Crystal structure of the N-terminal region of human Ash2L shows a winged-helix motif involved in DNA binding. EMBO Rep, 12, 797-803.
7. Chen, Y., Rai, R., Zhou, Z.R., Kanoh, J., Ribeyre, C., Yang, Y., Zheng, H., Damay, P., Wang, F., Tsujii, H.，Hiraoka, Y., Shore, D., Hu, H.Y., Chang, S., and Lei, M. (2011) A conserved motif within RAP1 has diversified roles in telomere protection and regulation in different organisms. Nat Struct Mol Biol, 18, 213-221.
8. Zeng, Z., Wang, W., Yang, Y., Chen, Y., Yang, X., Diehl, J.A., Liu, X. and Lei, M. (2010) Structural basis of selective ubiquitination of TRF1 by SCFFbx4. Dev Cell, 18, 214-225.
9. Wang, F., Yang, Y., Singh, T.R., Busygina, V., Guo, R., Wan, K., Wang, W., Sung, P., Meetei, A.R. and Lei, M. (2010) Crystal structures of RMI1 and RMI2, two OB-fold regulatory subunits of the BLM complex. Structure, 18, 1159-1170.
10. Cao, F., Chen, Y., Cierpicki, T., Liu, Y., Basrur, V., Lei, M. and Dou, Y. (2010) An Ash2L/RbBP5 heterodimer stimulates the MLL1 methyltransferase activity through coordinated substrate interactions with the MLL1 SET domain. PLoS One, 5, e14102.
11. Sun, J., Yu, E.Y., Yang, Y., Confer, L.A., Sun, S.H., Wan, K., Lue, N.F. and Lei, M. (2009) Stn1-Ten1 is an Rpa2-Rpa3-like complex at telomeres. Genes Dev, 23, 2900-2914.
12. Yu, E.Y., Wang, F., Lei, M. and Lue, N.F. (2008) A proposed OB-fold with a protein-interaction surface in Candida albicans telomerase protein Est3. Nat Struct Mol Biol, 15, 985-989.
13. Sowd, G., Lei, M. and Opresko, P.L. (2008) Mechanism and substrate specificity of telomeric protein POT1 stimulation of the Werner syndrome helicase. Nucleic Acids Res, 36, 4242-4256.
14. Chen, Y., Yang, Y., van Overbeek, M., Donigian, J.R., Baciu, P., de Lange, T. and Lei, M. (2008) A shared docking motif in TRF1 and TRF2 used for differential recruitment of telomeric proteins. Science, 319, 1092-1096.
15. Wang, F., Podell, E.R., Zaug, A.J., Yang, Y., Baciu, P., Cech, T.R. and Lei, M. (2007) The POT1-TPP1 telomere complex is a telomerase processivity factor. Nature, 445, 506-510.
16. Chen, Y., Yang, Y., Wang, F., Wan, K., Yamane, K., Zhang, Y. and Lei, M. (2006) Crystal structure of human histone lysine-specific demethylase 1 (LSD1). Proc Natl Acad Sci U S A, 103, 13956-13961.
17. Opresko, P.L., Mason, P.A., Podell, E.R., Lei, M., Hickson, I.D., Cech, T.R. and Bohr, V.A. (2005) POT1 stimulates RecQ helicases WRN and BLM to unwind telomeric DNA substrates. J Biol Chem, 280, 32069-32080.
18. Lei, M., Zaug, A.J., Podell, E.R. and Cech, T.R. (2005) Switching human telomerase on and off with hPOT1 protein in vitro. J Biol Chem, 280, 20449-20456.
19. Lei, M., Robinson, M.A. and Harrison, S.C. (2005) The active conformation of the PAK1 kinase domain. Structure, 13, 769-778.
20. M., Podell, E.R. and Cech, T.R. (2004) Structure of human POT1 bound to telomeric single-stranded DNA provides a model for chromosome end-protection. Nat Struct Mol Biol, 11, 1223-1229.
21. Lei, M., Podell, E.R., Baumann, P. and Cech, T.R. (2003) DNA self-recognition in the structure of Pot1 bound to telomeric single-stranded DNA. Nature, 426, 198-203.
22. Parrini, M.C., Lei, M., Harrison, S.C. and Mayer, B.J. (2002) Pak1 kinase homodimers are autoinhibited in trans and dissociated upon activation by Cdc42 and Rac1. Mol Cell, 9, 73-83.
23. Lei, M., Baumann, P. and Cech, T.R. (2002) Cooperative binding of single-stranded telomeric DNA by the Pot1 protein of Schizosaccharomyces pombe. Biochemistry, 41, 14560-14568.
24.. Lei, M., Lu, W., Meng, W., Parrini, M.C., Eck, M.J., Mayer, B.J. and Harrison, S.C. (2000) Structure of PAK1 in an autoinhibited conformation reveals a multistage activation switch. Cell, 102, 387-397.