Publications
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Zhang, Qindong; Olberg, Anniken & Sioud, Mouldy
(2022).
Structural requirements for the binding of a peptide to prohibitins on the cell surface of monocytes/macrophages.
International Journal of Molecular Sciences.
ISSN 1661-6596.
23(8).
doi:
10.3390/ijms23084282.
Full text in Research Archive
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Sioud, Mouldy; Juzenas, Petras; Zhang, Qindong; Kleinauskas, Andrius & Qian, Peng
(2021).
Evaluation of in vitro phototoxicity of a minibody-ir700 conjugate using cell monolayer and multicellular tumor spheroid models.
Cancers.
13(13).
doi:
10.3390/cancers13133356.
Full text in Research Archive
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Zegarra, Sergio Miguel Castaneda; Zhang, Qindong; Alirezaylavasani, Amin; Berrocal, Marion Fernandez; Yao, Rouan & Oksenych, Valentyn
(2020).
Leaky severe combined immunodeficiency in mice lacking non-homologous end joining factors XLF and MRI.
Aging.
12(23),
p. 23578–23597.
doi:
10.18632/aging.202346.
Full text in Research Archive
Show summary
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 function of downstream factors PAXX, MRI, DNA-PKcs, Artemis, XLF, XRCC4, and LIG4. Mutations in several known NHEJ genes result in severe combined immunodeficiency (SCID). Inactivation of Mri, Paxx or Xlf in mice results in normal or mild phenotype, while combined inactivation of Xlf/Mri, Xlf/Paxx, or Xlf/Dna-pkcs leads to late embryonic lethality. Here, we describe three new mouse models. We demonstrate that deletion of Trp53 rescues embryonic lethality in mice with combined deficiencies of Xlf and Mri. Furthermore, Xlf-/-Mri-/-Trp53+/- and Xlf-/-Paxx-/-Trp53+/- mice possess reduced body weight, severely reduced mature lymphocyte counts, and accumulation of progenitor B cells. We also report that combined inactivation of Mri/Paxx results in live-born mice with modest phenotype, and combined inactivation of Mri/Dna-pkcs results in embryonic lethality. Therefore, we conclude that XLF is functionally redundant with MRI and PAXX during lymphocyte development in vivo. Moreover, Mri genetically interacts with Dna-pkcs and Paxx.
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Zegarra, Sergio Miguel Castaneda; Huse, Camilla; Røsand, Øystein; Sarno, Antonio; Xing, Mengtan & Gago-Fuentes, Raquel
[Show all 14 contributors for this article]
(2019).
Generation of a mouse model lacking the non-homologous end-joining factor Mri/Cyren.
Biomolecules.
9:798(12),
p. 1–13.
doi:
10.3390/biom9120798.
Full text in Research Archive
Show summary
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 V(D)J recombination in developing B and T lymphocytes, and for class switch recombination in mature B cells. The Ku heterodimer formed by Ku70 and Ku80 recognizes DSBs and facilitates the recruitment of accessory factors (e.g., DNA-PKcs, Artemis, Paxx and Mri/Cyren) and downstream core factor subunits X-ray repair cross-complementing group 4 (XRCC4), XRCC4-like factor (XLF), and DNA ligase 4 (Lig4). Accessory factors might be dispensable for the process, depending on the genetic background and DNA lesion type. To determine the physiological role of Mri in DNA repair and development, we introduced a frame-shift mutation in the Mri gene in mice. We then analyzed the development of Mri-deficient mice as well as wild type and immunodeficient controls. Mice lacking Mri possessed reduced levels of class switch recombination in B lymphocytes and slow proliferation of neuronal progenitors when compared to wild type littermates. Human cell lines lacking Mri were as sensitive to DSBs as the wild type controls. Overall, we concluded that Mri/Cyren is largely dispensable for DNA repair and mouse development.
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Published
Aug. 26, 2024 11:08 AM
- Last modified
Mar. 4, 2025 3:23 PM