Yong-jie Xu, M.D., Ph.D.

Pharmacology & Toxicology-SOM
Associate Professor, Pharmacology & Toxicology
Biological Sciences Bldg II 160, 3640 Colonel Glenn Hwy, Dayton, OH 45435-0001


M.D.: Peking Union Medical College/Chinese Academy of Medical Sciences

Ph.D.: Biochemistry, Cell and Molecular Biology Program, The Johns Hopkins University School of Medicine

Postdoctoral: Memorial Sloan-Kettering Cancer Center

Research Interests

Understanding how genomic stability 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 DNA replication forks become unstable and may undergo catastrophic collapse, leading to mutagenic chromosomal DNA damage or cell death. For this reason, defects in the DNA replication checkpoint are known causes of genomic instability and cancer.

The research interest of my lab is to understand the signaling mechanism of the DNA replication checkpoint (also called the S phase or intra-S phase checkpoint) when replication is perturbed by various endogenous or exogenous factors. The checkpoint senses the perturbations and activates a series of coordinated protective cellular responses such as cell cycle delay, increased production of dNTPs, and protection of perturbed forks from collapsing so that DNA synthesis can resume when perturbations diminish. The long-term goal of our research is to understand how checkpoint signaling is initiated at the perturbed replication forks and how perturbed forks are protected by the activated checkpoint. We use the fission yeast S. pombe as the primary model for this study because it is a well-established system for studying the cellular mechanisms that are conserved in higher eukaryotes, including humans. In addition, the checkpoint signaling pathways in fission yeast are relatively linear, which promotes an unambiguous description of the signaling mechanisms.  We believe that progress in this study will advance our knowledge about how genomic integrity is maintained over generations and how it can be disrupted in eukaryotic cells. It may also provide therapeutic benefits for cancer chemotherapy designed to interfere with DNA replication or the checkpoint signaling in tumor cells.

Based on our recent unexpected genetic data, we are also working on the combination therapies that are based on the clinically used drug hydroxyurea. Hydroxyurea perturbs DNA replication and activates the replication checkpoint in all eukaryotic organisms. We hope that the drug combinations can be useful for the treatment of cancer or fungal infections.

My lab is located in room 156 and 158 and the office is in room 160, Biological Sciences Building-II.  We are recruiting talented graduate students and motivated post-doctoral fellows to join the lab and conduct exciting research.


  1. Davi K, Yurtsever I, and Xu YJ (2023) A missense mutation in the suc22 gene encoding the small subunit of ribonucleotide reductase significantly sensitizes fission yeast to chronic treatment with hydroxyurea. MicroPublication-BIOLOGY https://micropublication.org/journals/biology/micropub-biology-001041
  2. Dev K, Yurtsever I, Bhadra S, Guduri YA, Davi K, and Xu YJ (2023) Dissecting the cell-killing mechanisms of hydroxyurea using spot assays. Methods in Molecular Biology. Springer Nature (in press)
  3. Bhadra S and Xu YJ (2023) TTT(Tel2-Tti1-Tti2) complex, the co-chaperone of PIKKs and a potential target for cancer chemotherapy. Int. J. Mol. Sci. 24(9), 8268.  https://doi.org/10.3390/ijms24098268
  4. Xu YJ, Bhadra S, Mahadi ATA, Dev K, Yurtsever I, and Nakamura TM (2023) Comprehensive mutational analysis of the checkpoint function of Rpa1/Ssb1 in fission yeast. PLOS Genet. 19(5): e1010691. https://doi.org/10.1371/journal.pgen.1010691
  5. Khan S, Ahamad N, Bhadra S, Xu Z, and Xu YJ (2022) Smc5/6 complex promotes Rad3ATR checkpoint signaling at the perturbed replication fork through sumoylation of the RecQ helicase Rqh1. Mol. Cell. Biol. 42(6) https://journals.asm.org/doi/10.1128/mcb.00045-22. (This paper is featured on the journal cover).
  6. Alyahya MY, Khan S, Bhadra S, Samuel RE, and Xu YJ (2022) Replication stress induced by the ribonucleotide reductase inhibitor guanazole, triapine, and gemcitabine in fission yeast. FEMS Yeast Res. V22, issue 1 https://academic.oup.com/femsyr/article/22/1/foac014/6545798.
  7. Zhang L, Geng, XR, Wang FF, Tang JS, Ichida Y, Arishya S, Jin S, Chen MY, Tang ML, Pozo FM, Wang WX, Wang J, Wozniak M, Guo XX, Miyagi M, Jin FL, Xu YJ, Yao XS, and  Zhang YW (2022). 53BP1 regulates heterochromatin through liquid phase separation. Nature Commun. 13:360 https://doi.org/10.1038/s41467-022-28019-y
  8. Ahamad N, Khan S, Mahdi ATA, and Xu YJ (2021) Checkpoint functions of RecQ helicases at perturbed DNA replication fork. Curr. Genet. https://doi.org/10.1007/s00294-020-01147-y
  9. Ahamad N, Khan S, and Xu YJ (2020) RecQ DNA helicase Rqh1 promotes Rad3ATR kinase signaling in the DNA replication checkpoint pathway of fission yeast. Mol. Cell. Biol. 40(7) e00145-20 https://mcb.asm.org/content/40/17/e00145-20.
  10. Xu YJ, Khan S, Didier AC, Wozniak M, Liu YF, Singh S, and Nakamura TM (2019) A tel2 mutation that destabilizes the Tel2-Tti1-Tti2 complex eliminates Rad3ATR kinase signaling in the DNA replication checkpoint and leads to telomere shortening in fission yeast. Mol. Cell. Biol. 39(20) e00175-19 https://mcb.asm.org/content/early/2019/07/22/MCB.00175-19
  11. Singh A, Agarwal A, and Xu YJ (2017) Novel cell-killing mechanisms of hydroxyurea and the implications towards combination therapy for the treatment of fungal infections. Antimicrobiol. Agents Chemother. 61(11) e00374-17. http://aac.asm.org/content/61/11/e00734-17.full
  12. Singh A and Xu YJ (2017) Heme deficiency sensitizes yeast cells to oxidative stress induced by hydroxyurea.  J. Biol. Chem. 292(22) 9088-9103  http://www.jbc.org/content/292/22/9088.full.pdf?sid=da7da422-77f3-4c08-8...
  13. Xu YJ, Singh A, and Alter GM (2016) Hydroxyurea induces cytokinesis arrest in cells expressing a mutated sterol-14α-demethylase in the ergosterol biosynthesis pathway. Genetics 240, 959-973   http://www.genetics.org/content/204/3/959?etoc
  14. Singh A and Xu YJ (2016) The cell killing mechanisms of hydroxyurea Genes 7, 99  http://www.mdpi.com/2073-4425/7/11/99.
  15. Xu YJ (2016) Inner nuclear membrane protein Lem2 facilitates Rad3-mediated checkpoint signaling under replication stress induced by nucleotide depletion in fission yeast. Cell. Signal. 28, 235-245    http://www.sciencedirect.com/science/article/pii/S0898656815300140
  16. 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    http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0092936
  17. 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.    http://femsyr.oxfordjournals.org/content/12/4/486.long
  18. 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. http://www.jbc.org/content/286/26/22864.long
  19. Xu YJ and Leffak, M (2010) ATRIP from TopBP1 to ATR – in vitro activation of a DNA damage checkpoint. Proc. Natl. Acad. Sci. USA. 107:13561-13562 (co-correspondence author). http://www.pnas.org/content/107/31/13561.long
  20. Xu YJ and Kelly TJ (2008) Autoinhibition and Activation of the DNA replication checkpoint kinase Cds1. J. Biol. Chem. 284:16016-16027 (co-corresponding author). http://www.jbc.org/content/284/23/16016.long
  21. Xu YJ, Davenport M, and Kelly TJ (2006b) Two-stage mechanism for activation of the DNA replication checkpoint kinase Cds1 in fission yeast. Genes & Dev. 20:990-2003.   http://genesdev.cshlp.org/content/20/8/990.long
  22. Xu YJ, DeMott MS, Hwang JJ, Greenberg MM, and Demple B (2003) Action of human apurinic endonuclease (Ape1) on C1’-oxidized deoxyribose damage in DNA. DNA Repair 2:175-185.    http://www.sciencedirect.com/science/article/pii/S1568786402001945
  23. Xu YJ, Kim E, and Demple B (1998) Excision of C4’-oxidized deoxyribose lesions from double-stranded DNA by human apurinic endonuclease (Ape1 protein) and DNA polymerase ß. J. Biol. Chem. 273:28837-28844.   http://www.jbc.org/content/273/44/28837.long
  24. Demple B, Bailey E, Bennett RAO, Masuda Y, Wong D, and 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.  http://link.springer.com/chapter/10.1007%2F978-1-4615-4865-2_6#page-1
  25. Xu YJ, Xi Z, Zhen YS, and Goldberg IH (1997a) Mechanism of formation of novel covalent drug.DNA interstrand cross-links and monoadducts by enediyne antitumor antibiotics. Biochemistry 36:14975-14984.  http://pubs.acs.org/doi/abs/10.1021/bi972101o
  26. Xu YJ, Zhen YS, and Goldberg IH (1997b) Enediyne C1027 induces the formation of novel covalent DNA interstrand cross-links and monoadducts. J. Am. Chem. Soc. 119:1133-1134. http://pubs.acs.org/doi/abs/10.1021/ja963444x  Note: C1027 is now renamed as Lidamycin (力达霉素). It is the first structurally new antitumor antibiotic discovered in China
  27. Goldberg IH, Kappen LS, Xu YJ, Stassinopoulos A, Zeng XP, Xi Z, and 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. ISBN: 9780792340256
  28. Xu YJ, Zhen YS, and 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.    http://pubs.acs.org/doi/abs/10.1021/bi00038a044
  29. Xu YJ, Zhen YS, and Goldberg IH (1994) C1027 chromophore, a new enediyne antitumor antibiotic, induces sequence-specific double-strand DNA cleavage. Biochemistry 33:5947-5953.       http://pubs.acs.org/doi/abs/10.1021/bi00185a036
  30. Xu YJ, Li DD, and 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) (中国科学 化学) 8:814-819.   http://chem.scichina.com:8081/sciB/CN/Y1992/V22/I8/814
  31. Xu YJ, Li DD, and Zhen YS (1991) Recent advances in the research of macromolecular antitumor antibiotics. Chin. J. Antibiot. (中国抗生素杂志) 6:470-475.
  32. Xu YJ, Li DD, and 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.    http://link.springer.com/article/10.1007/BF00689274
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