Wei Xiao’s Homepage

 
 

Ubiquitin (Ub) is an abundant, ubiquitous and highly-conserved small protein (76 amino acids) found in all eukaryotic cells, from unicellular yeasts to human.  Through a series of enzymatic reactions, Ub is attached to the target protein with the help of an Ub conjugating enzyme (E2 or Ubc) and an Ub ligase (E3), followed by the formation of a multimeric Ub chain known as the poly-Ub chain.  Target proteins attached by poly-Ub are sent for degradation by the 26S proteosome, and this process serves as an important means of regulation involved in numerous cellular activities.  Its importance is appreciated by the 2004 Nobel Prize award to the discovery of ubiquitination and its involvement in the target protein degradation.  Careful investigation reveals that the above Ub chain is formed via a surface Lys48 residue of an incoming Ub attached to the C-terminal Gly residue.  It was subsequently found that the Ub chain can also be formed via a surface Lys63 residue.  Among over a dozen of Ubcs found in any organisms, only one, Ubc13, is capable of linking Ub through Lys63.  The unique feature of Ubc13 is due to its binding to another protein known as Uev (Ubc enzyme variant), which is also absolutely required for the process.  More importantly, proteins attached by Lys63-linked Ub are not targeted for degradation, but for altering activities.  Furthermore, among other types of ubiquitination, mono-ubiquitination is also believed to be a novel regulatory mechanism of the target protein activity, which expands the horizon of ubiquitination functions.  My laboratory is primarily interested in the discovery of above non-conventional ubiquitinaiton processes and in defining the molecular mechanisms of the related pathways.  Since a few well characterized non-conventional ubiquitination target proteins are involved in cellular metabolisms such as DNA damage tolerance, cell cycle checkpoint, innate immunity and stress response, and that these processes play critical roles in human diseases like cancer, this study will have direct impacts on the diagnosis and treatment of diseases including cancer.

 

Research Interests

Dr. Wei Xiao, Professor
Department of Microbiology and Immunology


Health Sciences Building
107 Wiggins Road
University of Saskatchewan
Saskatoon, Saskatchewan
Canada S7N 5E5


Phone:

  1. (306) 966-4308 (office)

  2. (306) 966-4309 (lab)

Fax:

  1. (306) 966-4298

E-mail:

  1. wei.xiao@usask.ca



Education:

B.Sc. (1982) Nanjing Agricultural University

M.Sc. (1984) University of Toronto

Ph.D. (1988) University of Saskatchewan

PDF (1990-1992) Harvard University


Honours and Awards:

University of Saskatchewan

Distinguished Researcher of the Year Award (2008)

College of Medicine Graduate Student Society (CMGSS), U. of Sask. Supervisor of the Year Award (2007)

Biographee, CANADA at the Millennium (2000)

Biographee, Canadian Who’s Who (since 1996)


Wu, Z., Shen, S., Zhang, Z., Zhang, W. and Xiao, W. (2014) Ubiquitin-conjugating enzyme complex Uev1A-Ubc13 promotes breast cancer metastasis through nuclear factor-κB mediated matrix metalloproteinase-1 gene regulation. Breast Cancer Res. 16: R75. [Text]

Cao, L., Tang, X., Zhang, X., Zhang, J., Tian, X., Wang, J., Xiong, M. and Xiao, W. (2014) Two-stage transcriptional reprogramming in Saccharomyces cerevisiae for optimizing ethanol production from xylose. Metab. Eng. 24: 150-159. [Text]

Ball, L.G., Xu, X., Blackwell, S., Hanna, M.D., Lambrecht, A.D. and Xiao, W. (2014) The Rad5 helicase activity is dispensable for error-free DNA post-replication repair. DNA Repair 16: 74-83. [Text]

Qin, Z., Lu, M., Xu, X., Hanna, M., Shiomi, N. and Xiao, W. (2013) DNA-damage tolerance mediated by PCNA•Ub fusions in human cells is dependent on Rev1 but not Polη. Nucleic Acids Res. 41: 7356-7369. [Text]

Bhat, A., Andersen, P.L., Qin, Z. and Xiao, W. (2013) The Rev3 subunit of Polζ is required for maintaining fragile site stability in human cells. Nucleic Acids Res. 41: 2328-2339. [Text]

Wei, T., Zhang, C., Xu, X., Hanna, M., Zhang, X., Wang, Y., Dai, H. and Xiao, W. (2013) Construction and evaluation of two biosensors based on yeast transcriptional response to genotoxic chemicals. Biosensors and Bioelectronics. 44: 138-145. [Text]

Wen, R., Li, J., Xu, X., Cui, Z. and Xiao, W. (2012) Zebrafish Mms2 promotes K63-linked polyubiquitination and is involved in p53-mediated DNA-damage response. DNA Repair 11: 157-166. [Text]

Xiang, D., Yang, H., Venglat, P., Cao, Y., Wen, R., Ren, M., Stone, S., Wang, E., Wang, H., Xiao, W., Weijers, D., Berleth, T., Laux, T., Selvaraj, G., Datla, R. (2011) POPCORN functions in the auxin pathway to regulate embryonic body plan and meristem organization in Arabidopsis. Plant Cell 23: 4348-4367. [Text]

Andersen, P.L., Xu, F., Ziola, B., McGregor, W.G. and Xiao, W. (2011) Sequential assembly of translesion DNA polymerases at UV-induced DNA damage sites. Mol. Biol. Cell. 22: 2373-2383.  [Text]

Wang, S., Wen, R., Shi, X., Lambrecht, A., Wang. H. and Xiao, W. (2011) RAD5A and REV3 constitute two alternative mechanisms of DNA damage tolerance in Arabidopsis. DNA Repair 10: 620-628. [Text]

Zhang, M., Zhang, C., Li, J., Hanna, M., Zhang, X., Dai, H. and Xiao, W. (2011) Inactivation of YAP1 enhances sensitivity of the yeast RNR3-lacZ genotoxicity testing system to a broad range of DNA-damaging agents. Tox. Sci. 120: 310-321. [Text]

Markin, C.J., Saltibus, L., Kean, M., McKay, R., Xiao, W. and Spyracopoulos, L. (2010) Catalytic proficiency of ubiquitin conjugation enzymes: balancing pKa suppression, entropy, and electrostatics. J. Am. Chem. Soc. 132: 17775-17786. [Text]

Pastushok, L., Hanna, M. and Xiao, W. (2010) Constitutive fusion of ubiquitin to PCNA provides DNA damage tolerance independent of translesion polymerase activities. Nucleic Acids Res. 38: 5047-5058. [Text]


Markin, C.J., Xiao, W. and Spyracopoulos, L. (2010) Mechanism for recognition of polyubiquitin chains: balancing affinity through interplay between multivalent binding and dynamics.  J. Am. Chem. Soc. 132: 11247-11258. [Text]


Zhang, M., Hanna, M., Li, J., Butcher, S., Dai, H. and Xiao, W. (2010) Creation of a hyperpermeable yeast strain to genotoxic agents through combined inactivation of PDR and CWP genes. Tox. Sci. 113: 401-411. [Text]

Ball, L.G., Zhang, K., Cobb, J.A., Boone, C. and Xiao, W. (2009) The yeast Shu complex couples error-free PRR to homologous recombination. Mol. Microbiol. 73: 89-102. [Text]

Fu, Y., Pastushok, L. and Xiao, W. (2008) DNA damage-induced gene expression in Saccharomyces cerevisiae. FEMS Microbol. Rev. 32: 908-926. [Text]

Huen, M.S.Y., Yuan, J., Yamamoto, M., Akira, S., Ashley, C., Xiao, W. and Chen, J. (2008) Noncanonical E2 variant-independent function of UBC13 in promoting checkpoint protein assembly. Mol. Cell. Biol. 19: 6104-6112. [Text]

Anderson, H.J., Vonarx, E.J., Pastushok, L., Nakagawa, M., Katafuchi, A., Gruz, P., Di Rubbo, A., Grice, D.M., Osmond, M.J., Sakamoto, A., Nohmi, T., Xiao, W. and Kunz, B.A. (2008) Arabidopsis thaliana Y-family DNA polymerase η catalyses translesion synthesis and interacts functionally with PCNA2. Plant J. 55: 895-908. [Text]

Fu, Y., Zhu, Y. Zhang, K., Yeung, M., Durocher, D. and Xiao, W. (2008) Rad6-Rad18 mediates a eukaryotic SOS response by ubiquitinating the 9-1-1 checkpoint clamp. Cell 133: 601-611. [Text]

Zhang, M., Liang, Y., Zhang, X., Xu, Y., Dai, H. and Xiao, W. (2008) Deletion of yeast CWP genes enhances cell permeability to genotoxic agents. Toxicol. Sci. 103: 68-76. [Text]

Wen, R., Torres-Acosta, J.A., Pastushok, L., Lai, X., Pelzer, L., Wang, H. and Xiao, W. (2008) Arabidopsis UEV1D promotes lysine-63-linked polyubiquitination and is involved in DNA damage response. Plant Cell 20: 213-227. [Text]

Andersen, P.L., Xu, F. and Xiao, W. (2008) Eukaryotic DNA damage tolerance and translesion synthesis through covalent modifications of PCNA. Cell Res. 18: 162-173. [Text]

Barbour, L., Ball, L.G., Zhang, K. and Xiao, W. (2006) DNA damage checkpoints are involved in postreplication repair. Genetics 174: 1789-1800. [Text]

Syed, N.A., Andersen, P.L., Warrington, R.C. and Xiao, W. (2006) Uev1A, a ubiquitin conjugating enzyme variant, inhibits stress-induced apoptosis through NF-κB activation. Apoptosis 11: 2147-2157. [Text]

Fu, Y. and Xiao, W. (2006) Identification and characterization of CRT10 as a novel regulator of Saccharomyces cerevisiae ribonucleotide reductase genes. Nucleic Acids Res. 34: 1876-1883. [Text]

Barbour, L. and Xiao, W. (2006) Mating type regulation of cellular tolerance to DNA damage is specific to the DNA postreplication repair and mutagenesis pathway. Mol. Microbiol. 59: 637-650. [Text]

Andersen, P., Zhou, H., Pastushok, L., Moraes, T., McKenna, S., Ziola, B., Ellison, M.J., Dixit, V.M. and Xiao, W. (2005) Distinct regulation of Ubc13 functions by two Uev proteins Mms2 and Uev1A. J. Cell Biol. 170: 745-755. [Text]

Pastushok, L., Moraes, T.F., Ellison, M.J. and Xiao, W. (2005) A single Mms2 "key" residue insertion into a Ubc13 pocket determines the interface specificity of a human Lys63 ubiquitin conjugation complex. J. Biol. Chem. 280: 17891-17900. [Text]

Zhu, Y and Xiao, W. (2004) Pdr3 is required for DNA damage induction of MAG1 and DDI1 via a bi-directional promoter element. Nucleic Acids Res. 32: 5066-5075. [Text]

Zhou, H., Wertz, I., O'Rourke, K., Ultsch, M., Seshagiri, S., Eby, M., Xiao, W. and Dixit, V.M. (2004) Bcl10 activates the NF-κB pathway through ubiquitination of NEMO. Nature 427: 167-171. [Text]

Hanna, M.D., Meadows, K.L., Chow, B.L., Jinks-Robertson, S., Doetsch, P.W. and Xiao, W. (2004) Involvement of two endonuclease III homologs in the base excision repair for the processing of DNA alkylation damage in Saccharomyces cerevisiae. DNA Repair 3: 51-59 [Text]

Fu, Y. and Xiao, W. (2003) Functional domains required for the Saccharomyces cerevisiae Mus81-Mms4 endonuclease complex formation and nuclear localization. DNA Repair 2: 1435-1447 [Text]

Jia, X. and Xiao, W. (2003) Compromised DNA repair enhances sensitivity of the RNR3-lacZ genotoxic testing system. Toxicol. Sci. 75: 82-88. [Text]

McKenna, S., Moraes, T., Pastushok, L., Ptak, C., Xiao, W., Spyracopoulos, L. and Ellison, M.J. (2003) An NMR based model of the ubiquitin-bound human ubiquitin conjugation complex Mms2/Ubc13: The structural basis for lysine 63 chain catalysis. J. Biol. Chem. 278: 13151-13158. [Text]

Brown, M., Zhu, Y., Hemmingsen, S, and Xiao, W. (2002) Structural and functional conservation of error-free postreplication repair in Schizosaccharomyces pombe. DNA Repair 1: 869-880. [Text]

Li, Z., Xiao, W., McCormick, J.J. and Maher, V.M. (2002) Identification of a protein essential for a major pathway used by human cells to avoid UV-induced DNA damage. Proc. Natl. Acad. Sci. USA 99: 4459-4464. [Text]

Broomfield, S. and Xiao, W. (2002) Suppression of genetic defects within the RAD6 pathway by srs2 is specific for error-free postreplication repair but not for damage induced mutagenesis. Nucleic Acids Res. 30: 732-739. [Text]

McKenna, S., Spyracopoulos, L., Moraes, T., Pastushok, L., Ptak, C., Xiao, W. and Ellison, M.J. (2001) Non-covalent interaction between ubiquitin and the human DNA repair protein Mms2 is required for Ubc13-mediated poly-ubiquitination. J. Biol. Chem. 276: 40120-40126. [Text]

Moraes, T.F., Edwards, R.A., McKenna, S., Pastushok, L., Xiao, W., Glover, J.N.M. and Ellison, M.J. (2001) Crystal structure of the human ubiquitin conjugating enzyme complex, hMms2-hUbc13. Nature Structural Biol. 8: 669-673. [Text]

Xiao, W., Chow, B.L., Broomfield, S. and Hanna, M. (2000) The Saccharomyces cerevisiae RAD6 group is composed of an error-prone and two error-free postreplication repair pathways. Genetics 155: 1633-1641. [Text]

Chamankhah, M., Fontanie, T. and Xiao, W. (2000) The Saccharomyces cerevisiae mre11(ts) allele confers a separation of DNA repair and telomere maintenance functions. Genetics 155: 569-576. [Text]

Selected Recent Publications (full list)