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Imaging the cellular response to an antigen tagged interstrand crosslinking agent

  1. Author:
    Bellani, Marina A
    Huang, Jing
    Zhang, Jing
    Gali,Himabindu
    Thazhathveetil, Arun Kalliat
    Pokharel, Durga
    Majumdar, Ishani
    Shaik, Althaf
    Seidman, Michael M
  2. Author Address

    Laboratory of Molecular Biology and Immunology, NIA, NIH, Baltimore MD 21224, USA., State Key Laboratory of Chemo/Biosensing and Chemometrics, School of Biomedical Sciences, Hunan University, Changsha 410082, China., Department of Neurosurgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China., Frederick National Laboratory for Cancer Research, Frederick, MD 21703, USA., Nitto Denko Avecia Inc., Cincinnati, OH 45215, USA., Horizon Discovery, Lafayette, CO 80026, USA., Laboratory of Molecular Biology and Immunology, NIA, NIH, Baltimore MD 21224, USA. Electronic address: seidmanm@grc.nia.nih.gov.,
    1. Year: 2023
    2. Date: Jun 09
    3. Epub Date: 2023 06 09
  1. Journal: DNA Repair
    1. 128
    2. Pages: 103525
  2. Type of Article: Article
  3. Article Number: 103525
  1. Abstract:

    Immunofluorescence imaging is a standard experimental tool for monitoring the response of cellular factors to DNA damage. Visualizing the recruitment of DNA Damage Response (DDR) components requires high affinity antibodies, which are generally available. In contrast, reagents for the display of the lesions that induce the response are far more limited. Consequently, DDR factor accumulation often serves as a surrogate for damage, without reporting the actual inducing structure. This limitation has practical implications given the importance of the response to DNA reactive drugs such as those used in cancer therapy. These include interstrand crosslink (ICL) forming compounds which are frequently employed clinically. Among them are the psoralens, natural products that form ICLs upon photoactivation and applied therapeutically since antiquity. However, despite multiple attempts, antibodies against psoralen ICLs have not been developed. To overcome this limitation, we developed a psoralen tagged with an antigen for which there are commercial antibodies. In this report we describe our application of the tagged psoralen in imaging experiments, and the unexpected discoveries they revealed. Published by Elsevier B.V.

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External Sources

  1. DOI: 10.1016/j.dnarep.2023.103525
  2. PMID: 37320956
  3. PII : S1568-7864(23)00079-4

Library Notes

  1. Fiscal Year: FY2022-2023
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