Qindong Zhang

Qindong Zhang
Norwegian University of Science and Technology | NTNU · Department of Cancer Research and Molecular Medicine

Master of Science

About

4
Publications
150
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8
Citations
Additional affiliations
July 2020 - present
Oslo University Hospital
Position
  • PhD Student

Publications

Publications (4)
Article
Full-text available
Non-homologous end-joining (NHEJ) is a DNA repair pathway required to detect, process, and ligate DNA double-stranded breaks (DSBs) throughout the cell cycle. The NHEJ pathway is necessary for V(D)J recombination in developing B and T lymphocytes. During NHEJ, Ku70 and Ku80 form a heterodimer that recognizes DSBs and promotes recruitment and functi...
Preprint
Full-text available
Non-homologous end-joining (NHEJ) is a DNA repair pathway required to detect, process, and ligate DNA double-stranded breaks (DSBs) throughout the cell cycle. The NHEJ pathway is necessary for V(D)J recombination in developing B and T lymphocytes. During NHEJ, Ku70 and Ku80 form a heterodimer that recognizes DSBs and promotes recruitment and functi...
Preprint
Full-text available
Non-homologous end joining (NHEJ) is a DNA repair pathway required to detect, process and ligate DNA double-stranded breaks (DSBs) throughout the cell cycle. The NHEJ pathway is required for the V(D)J recombination in developing B and T lymphocytes. During the NHEJ, the core factors Ku70 and Ku80 form a heterodimer called Ku, which recognizes DSBs...
Preprint
Full-text available
Classical non-homologous end joining (NHEJ) is a molecular pathway that detects, processes and ligates DNA double-strand breaks (DSBs) throughout the cell cycle. Mutations in several NHEJ genes result in neurological abnormalities and immunodeficiency both in humans and mice. The NHEJ pathway is required for the V(D)J recombination in developing B...

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Projects

Projects (2)
Project
Aim1. Generating of Mri.Dna-pkcs.Paxx triple knockout and Mri.Dna-pkcs and Mri.Paxx double-knockout models. Aim 2. Characterization of lymphocyte development in Mri.Paxx double knockout mouse model. Aim 3. Characterization of genomic stability in a triple and double knockout mouse models described in the Aim 1.
Project
The rationale for choosing the research question The Non-Homologous DNA End Joining (NHEJ) is the major pathway that is responsible for sensing and repairing DNA double-strand breaks (DSBs) throughout the cell cycle. Among others, the NHEJ repairs the DSBs generated during RAG mediated V(D)J recombination which is utilized by developing B and T lymphocytes to change the variable region of the immunoglobulin (Ig) molecules, increasing the possibility that the antibodies can recognize a wide variety of antigens and creating a diverse receptor repertoire. The NHEJ also participates in sensing and repairing the DSBs introduced during class switch recombination (CSR), which generates antibodies belonging to the heavy-chain classes other than IgM and IgD, in mature B lymphocytes. Ku70, Ku80, DNA ligase 4 (Lig4), and X-ray repair cross complementing protein 4 (XRCC4) are considered as the core NHEJ factors. Ku70 together with Ku80 forms a heterodimer, named “Ku”, which recognizes DSBs and provides binding sites for downstream NHEJ factors, while Lig4 and XRCC4 forms a protein complex, which mediates DSBs’ ligation. In addition, there are several accessary NHEJ factors, including XRCC4-like factor (XLF), paralogue of XRCC4 and XLF (PAXX), DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and the modulator of retrovirus infection (Mri), etc. Mutations in one or several NHEJ factors lead to phenotypes that associate with defective DSBs repair. Inability to repair RAG-mediated DSBs results in severe combined immunodeficiency (SCID). For example, mutations in DNA-PKcs1 in human or deficiency in Lig42 in mice results in SCID. NHEJ repairs clastogenic agents induced DSBs causing genomic instability which is the basis of certain types of cancer, e.g. medulloblastoma3. For instance, combined inactivation of Lig4 and pro-apoptotic factor Trp53 in mice results in medulloblastoma3. In spite of that, mutations in several NHEJ factors result in other phenotypes. Inactivation of Ku70 or Ku80 in mice leads to moderate level of p53-mediated apoptosis during cortical neurogenesis and growth retardation, although does not affect the embryonic survival rate. In contrast, inactivation of Lig4 or Xrcc4 in mice leads to neuronal apoptosis and late embryonic lethality, which can be rescued by Ku deficiency4. XLF shares similar structure with XRCC4, forming a heterodimer with XRCC4 to promote binding to Lig4 and enhance XRCC4/Lig4-mediated end-joining5. Compare to Lig4 or XRCC4, repair of RAG-mediated DSBs during lymphocyte development is robust in cells lacking XLF, and Xlf-deficient mice possess only modest phenotype, mildly-affected life-span of lymphocytes which can then be rescued by inactivation of Trp536. In addition, Paxx-deficient mice also exhibit mild phenotypes. However, combined inactivation of Xlf with Paxx