Yong-jie Xu, Ph.D.

Department:
Biochemistry/Molecular Biology-COSM
Title:
Assistant Professor, Biochemistry & Molecular Biology College of Science and Math
Address:
Diggs Laboratory 148, 3640 Colonel Glenn Hwy., Dayton, OH 45435
Phone:
937-775-4693
Education History: 

M.D.: 1991 Peking Union Medical College/Chinese Academy of Medical Sciences (Dian-dong Li & Yong-su Zhen)
Ph.D.: 2006 Biochemistry, Cell and Molecular Biology Program, Johns Hopkins University School of Medicine (Thomas J. Kelly)
Postdoctoral: Harvard Medical School (Irving H. Goldberg), Harvard School of Public Health (Bruce Demple) and Memorial Sloan-Kettering Cancer Center (Thomas J. Kelly)

Academics

Research statement: 

Understanding how eukaryotic genome integrity is maintained over generations – during which time the genome has to be accurately duplicated in each cell cycle – is one of the fundamental problems of modern biology. It is also a critical aspect of the more general problem of understanding the mechanisms that control cellular proliferation and prevent oncogenesis. The stability of the genome depends upon the precise operation of the DNA replication machinery and upon the checkpoint mechanism that deals with various perturbations of DNA replication. If undetected by the checkpoint, perturbed replication forks become unstable and may undergo catastrophic collapse, resulting in cell death or mutagenic chromosomal damage. For this reason, defects in the DNA replication checkpoint are known causes of genome instability and cancer.

My laboratory is interested in understanding the molecular mechanism of the replication checkpoint, a complex signaling pathway that is activated when DNA replication is perturbed. The checkpoint senses the perturbed DNA replication forks and elicits protective cellular responses such as cell cycle delay, stimulated production of deoxyribonucleotides, and more importantly, stabilization of perturbed forks against collapse so that normal DNA synthesis can resume when perturbations are eliminated. The long-term goal of the research program is to better understand the molecular interface between the DNA replication machinery and the checkpoint pathway in order to provide insights into how the checkpoint signaling is initiated at the perturbed replication forks and how perturbed forks are stabilized under stress, the two most prominent questions in the field. We use the fission yeast Schizosaccharomyces pombe as the primary working model organism because the signaling pathway of the replication checkpoint in fission yeast is relatively linear, which may provide an unambiguous description of the signaling mechanism. Progress in the study of the checkpoint signaling mechanism in fission yeast will ultimately advance our knowledge of how genome integrity is maintained and how it can be disrupted in all eukaryotic cells. It may also have implications to an improvement of chemotherapy designed to interfere with the DNA replication or the replication checkpoint in tumor cells.

We are located in the Diggs Research Laboratory Building. Talented graduate students and motivated post-doctoral fellows are welcome to join our research team.

Professional

Publications: 
  1. Yue M, Zeng L, Singh A, and Xu YJ (2014) Rad4 mainly functions in the Chk1-mediated DNA damage checkpoint pathway as a scaffold protein in Schizosaccharomyces pombe. PLoS ONE 9(3): e92936

  2. Wang Z, Kim, E, Leffak, M, and Xu YJ (2012) Treslin, DUE-B and GEMC1 cannot complement Sld3 mutants in fission yeast.  FEMS Yeast Res. 12, 486-490

  3. Yue M, Singh A, Wang Z and Xu YJ (2011) The phosphorylation network for efficient activation of the DNA replication checkpoint in fission yeast. J. Biol. Chem. 286:22864-22874.

  4. Xu YJ and Leffak, M (2010) ATRIP from TopBP1 to ATR – in vitro activation of a DNA damage checkpoint. Proc. Natl. Acad. Sci. U.S.A. 107:13561-13562 (co-corresponding author).

  5. Xu YJ, Kelly TJ (2008) Autoinhibition and Activation of the DNA replication checkpoint kinase Cds1. J. Biol. Chem. 284:16016-16027 (co-corresponding author).

  6. Xu YJ, Davenport M, Kelly TJ (2006b) Two-stage mechanism for activation of the DNA replication checkpoint kinase Cds1 in fission yeast. Genes & Dev. 20:990-2003

  7. Xu YJ, DeMott MS, Hwang JJ, Greenberg MM, Demple B (2003) Action of human apurinic endonuclease (Ape1) on C1’-oxidized deoxyribose damage in DNA.  DNA Repair 2:175-185

  8. Xu YJ, Kim E, Demple B (1998)  Excision of C4’-oxidized deoxyribose lesions from double-stranded DNA by human apurinic endonuclease (Ape1 protein) and DNA polymerase b. J. Biol. Chem. 273:28837-28844.

  9. Demple B, Bailey E, Bennett RAO, Masuda Y, Wong D, Xu YJ.  Roles of AP endonucleases in repair and genetic stability, in DNA Damage and Repair: Oxygen Radical Effects, Cellular Protection, and Biological Consequences. Ed. M. Dizdaroglu, Plenum Press, New York, 1998.

  10. Xu YJ, Xi Z, Zhen YS, Goldberg IH (1997a) Mechanism of formation of novel covalent drug.DNA interstrand cross-links and monoadducts by enediyne antitumor antibiotics. Biochemistry 36:14975-14984.

  11. Xu YJ, Zhen YS, Goldberg IH (1997b) Enediyne C1027 induces the formation of novel covalent DNA interstrand cross-links and monoadducts.  J. Am. Chem. Soc. 119:1133-1134

  12. Goldberg IH, Kappen LS, Xu YJ, Stassinopoulos A, Zeng XP, Xi Z, Yang CF (1995) Enediynes as probes of nucleic acid structure, in NATO Workshop on DNA cleavers and chemotherapy of cancer or viral diseases.  Ed. B. Meunnier, Kluwer, Dordrecht, The Netherlands.

  13. Xu YJ, Zhen YS, Goldberg IH (1995) A single binding mode of activated enediyne C1027 generates two types of double-strand DNA lesions: deuterium isotope-induced shuttling between adjacent nucleotide target sites.  Biochemistry 34:12451-12460.

  14. Xu YJ, Zhen YS, Goldberg IH (1994) C1027 chromophore, a new enediyne antitumor antibiotic, induces sequence-sepecific double-strand DNA cleavage.  Biochemistry 33:5947-5953.

  15. Xu YJ, Li DD, Zhen YS (1992) Molecular mechanism of C1027, a new antitumor antibiotic with highly potent cytotoxicity (Formation of abasic sites, single- and double-strand breaks in DNA and selective cleavage in the linker regions of nucleosomes).  Science in China (Series B) 8:814-819 (*co-corresponding author).

  16. Xu YJ, Li DD, Zhen YS (1991) Recent advances in the research of macromolecular antitumor antibiotics. Chin. J. Antibiot. 6:470-475.

  17. Xu YJ, Li DD, Zhen YS.  (1990) Mode of action of C1027, a new macromolecular antitumor antibiotic with highly potent cytotoxicity, on human hepatoma BEL-7402 cells.  Cancer Chemother. Pharmacol. 27:41-46.

     

     

     

     

     

     

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