Identification and characterization of novel Non-homologous end-joining (NHEJ) factors.

  • Li G, Alt FW, Cheng HL, Brush JW, Goff PH, Murphy MM, Franco S, Zhang Y, Zha S. Lymphocyte-Specific Compensation For XLF/Cernunnos End-Joining Functions In V(D)J Recombination. Molecular Cell 2008 Sep 5;31(5):631-40 PMCID: PMC2630261
  • Avagyan S, Churchill M, Yamamoto K, Crowe JL, Li C, Lee BJ, Zheng T, Mukherjee S, Zha S. Hematopoietic stem cell dysfunction underlies the progressive lymphocytopenia in XLF/Cernunnos deficiency. Blood 2014 Sep 4;124(10):1622-5. PMID: 25075129
  • Xing M, Yang M, Huo W, Feng F, Wei L, Jiang W, Ning S, Yan Z, Li W, Wang Q, Hou M, Dong C, Guo R, Gao G, Ji J, Zha S, Lan L, Liang H, Xu D. Interactome analysis identifies a new paralogue of XRCC4 (PAXX) in non-homologous end joining DNA repair pathway. Nat Commun. 2015 Feb 11;6:6233. PMID: 25670504
  • Liu X, Shao Z, Jiang W, Lee BJ, Zha S. PAXX promotes KU accumulation at DNA breaks and is essential for end-joining in XLF-deficient mice. Nat Commun. 2017 Jan 4;8:13816.PMID: 28051062
  • Hung PJ, Johnson B, Byrum A, Bredemeyer AL, Yewdell W, Johnson TE, Lee BJ, Deivasigamani S, Paull TT, Pisapia D, Chadhury D, Mosammaparast N, Amarasinghe GK, Zha S, Tyler JK and Sleckman BP MRI is a DNA Damage Response Adaptor during Classical Non-Homologous End Joining Molecular Cell (2018 in press)

Critical role of DNA damage response factors in DNA end-ligation in vivo.

  • Zha S, Sekiguchi J, Brush JW, Bassing CH, Alt FW. Complementary functions of ATM and H2AX in development and suppression of genomic instability. Proc Natl Acad Sci U S A.2008 Jul 8;105(27):9302-6. PMCID:PMC2453730
  • Zha S, Guo C, Boboila C, Oksenych V, Cheng HL, Zhang Y, Wesemann DR, Yuen G, Patel H, Goff PH, Dubois RL, Alt FW. ATM damage response and XLF repair factor are functionally redundant in joining DNA breaks. Nature. 2011 Jan 13;469(7329):250-4. PMCID: PMC3058373
  • Liu X, Jiang W, Dubois RL, Yamamoto K, Wolner Z, Zha S. Overlapping functions between XLF repair protein and 53BP1 DNA damage response factor in end joining and lymphocyte development. Proc Natl Acad Sci U S A. 2012 Mar 6;109(10):3903-8. PMCID: PMC3309750
  • Zhou Y, Lee JH, Jiang W, Crowe JL, Zha S, Paull TT. Regulation of the DNA Damage Response by DNA-PKcs Inhibitory Phosphorylation of ATM. Mol Cell. 2017 Jan 5;65(1):91-104. PMCID: PMC5724035

Inhibition ≠ Deletion: Kinase dependent structural function for ATM, DNA-PKcs and ATR.

  • Zha S, Jiang W, Fujiwara Y, Patel H, Goff PH, Brush JW, Dubois RL, Alt FW*. Ataxia telangiectasia-mutated protein and DNA-dependent protein kinase have complementary V(D)J recombination functions. Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2028-33. PMCID: PMC3033273
  • Yamamoto K, Wang Y, Jiang W, Liu X., Dubois RL, Ludwig T, Lin C, Bakkenist CJ., Zha S. Kinase-Dead ATM protein causes genomic instability and early embryonic lethality in mice. Journal of Cell Biology 2012 Aug 6;198(3):305-13 PMCID: PMC3413350
  • Jiang W, Crowe J, Liu X, Nakajima S, Wang Y, Li C, Lee BJ, Dubois RL, Liu C, Yu X, Lan L, Zha S. Differential phosphorylation of DNA-PKcs is the molecular control for end-processing and end-ligation during non-homologous end-joining. Molecular Cell 2015 Apr 2;58(1):172-85 PMID: 25818648.
  • Yamamoto K, Wang J, Sprinzen L, Xu J, Haddock CJ, Li C, Lee BJ, Loredan DG, Jiang W, Vindigni A, Wang D, Rabadan R, Zha S. Kinase-dead ATM protein is highly oncogenic and can be preferentially targeted by Topo-isomerase I inhibitors. Elife. 2016 Jun 15;5. PMID: 27304073
  • Menolfi, D, Jiang W, Lee BJ, Shao Z, Ester VM, Bakkenist CJ, Zha S. ATR inhibition differs from ATR loss by limiting the dynamic exchange of ATR and RPA on ssDNA filaments. Nature Communication 2018 (under review).

Molecular mechanism of oncogenic chromosomal translocations.

  • Zha S (Corresponding Author), Bassing CH, Sanda T, Brush JW, Patel H, Goff PH, Gatti R, Look AT, Alt FW. ATM-Deficient Thymic Lymphoma Is Associated With Aberrant TCRd Rearrangement And Gene Amplification. J Exp. Med 2010 Jul 5;207(7):1369-80 PMCID: PMC2901073
  • The BCL11B tumor suppressor is mutated across the major molecular subtypes of T-cell acute lymphoblastic leukemia.Gutierrez A, Kentsis A, Sanda T, Holmfeldt L, Chen SC, Zhang J, Protopopov A, Chin L, Dahlberg SE, Neuberg DS, Silverman LB, Winter SS, Hunger SP, Sallan SE, Zha S, Alt FW, Downing JR, Mullighan CG, Look AT. Blood. 2011 Oct 13;118(15):4169-73. Epub 2011 Aug 30. PMCID:PMC3204734
  • Jiang W, Lee BJ, Li C, Loredan DW and Zha S. Aberrant TCRδ rearrangement underlies the T cell lymphocytopenia and t(12;14) translocation associated with ATM deficiency. Blood 2015 Apr 23;125(17):2665-8 PMID: 25721125
  • Yamamoto K, Lee BJ, Li C, Dubois RL, Hobeika E, Bhagat G, Zha S. Early B-cell Specific Inactivation of ATM Synergizes with Ectopic CyclinD1 Expression to Promote Pre-germinal center B-cell Lymphomas in Mice. Leukemia. 2015 Jun;29(6):1414-24. PMID: 25676421

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