GFI1’s role in DNA repair suggests implications for tumour cell response to treatment
Authors:Charles Vadnais1 and Tarik Möröy1,2,3
1 Institut de recherches cliniques de Montréal (IRCM), Montréal, QC, Canada.
2 Département de microbiologie, infectiologie et immunologie, Université de Montréal.
3 Division of Experimental Medicine, McGill University, Montréal, QC, Canada.
Keywords:
GFI1, DNA repair, DNA damage response, PRMT1, MRE11, 53BP1, Cytarabine, tumour therapy.
Corresponding Author(s):
Conflict of interest statement:
The authors have no conflicts of interest to declare.
Please cite this article as:
Charles Vadnais and Tarik Möröy (2018). GFI1’s role in DNA repair suggests implications for tumour cell response to treatment. Cell Stress 2(8): 213-215. doi: 10.15698/cst2018.07.149
© 2018 Vadnais and Möröy. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
Despite recent advances in cancer treatment through personalized and precision medicine and new avenues such as immunotherapy and chimeric antibodies, the induction of DNA damage either through irradiation or specific compounds remains the primary approach to kill tumour cells. Improvements in our understanding of how tumour cells respond to DNA damage, and especially how this response differs from that of normal cells, are crucial to the development of better and more efficient therapies. We have recently shown that the activity of the oncogenic transcription factor GFI1, which is required for the development and maintenance of T and B cell leukemia, increases the ability of tumour cells to repair their DNA following damage (Vadnais et al. Nat Commun 9(1):1418). GFI1 accomplishes this by regulating the post-translational modifications (PTM) of key DNA repair proteins, including MRE11 and 53BP1, by the methyltransferase PRMT1. Here, GFI1 acts as an accessory protein required for the interaction between the enzyme and its substrates. This has implications for the treatment response of tumour cells overexpressing GFI1, which includes T cell leukemia, neuroendocrine lung carcinomas and aggressive subtypes of medulloblastoma, and suggests that targeting GFI1’s activity and with this its capacity to aid DNA repair may open avenues for new therapeutic approaches.