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Investigating the role of LncRNA H19 in DNA damage response
Thesis   Open access

Investigating the role of LncRNA H19 in DNA damage response

Britney Black
Master of Science (M.S.), Drexel University
Aug 2024
DOI:
https://doi.org/10.17918/00010719
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Abstract

DNA damage DNA damage response H19 LncRNA Aging
Long non-coding RNAs serve as diverse multifunctional regulators of gene expression within the cell and are associated with many age‐associated diseases. However, the function of lncRNAs in DNA damage response remains unclear. LncRNA H19, located downstream of the IGF2 gene locus on Chromosome 11, is a maternally imprinted gene that is highly conserved and critical in controlling embryonic growth. Studies have shown the loss of lncRNA H19 results in fetal overgrowth, while elevated H19 occurs in many human cancers. Our lab has shown H19 levels decline as cells undergo senescence and the depletion of H19 results in premature senescence via the H19/let7b/EZH2 axis. Specifically, during exposure to overwhelming cellular stress, repression of H19 is triggered by the loss of CTCF and prolonged activation of p53 as part of the senescence pathway. In this work, we characterize the role of lncRNA H19 in the senescent program and DNA damage response. Our results indicate increased levels of DNA damage markers with loss of H19 and an increase in DNA repair via NHEJ and HR by overexpression of H19.

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