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Alemi F, Raei Sadigh A, Malakoti F, et al. Molecular mechanisms involved in DNA repair in human cancers: An overview of PI3k/Akt signaling and PIKKs crosstalk. J Cell Physiol. 2021;doi: 10.1002/jcp.30573.
Alemi, F., Raei Sadigh, A., Malakoti, F., Elhaei, Y., Ghaffari, S. H., Maleki, M., Asemi, Z., Yousefi, B., Targhazeh, N., & Majidinia, M. (2021). Molecular mechanisms involved in DNA repair in human cancers: An overview of PI3k/Akt signaling and PIKKs crosstalk. Journal of cellular physiology, . https://doi.org/10.1002/jcp.30573
Alemi, Forough, et al. "Molecular mechanisms involved in DNA repair in human cancers: An overview of PI3k/Akt signaling and PIKKs crosstalk." Journal of cellular physiology vol. (2021). doi: https://doi.org/10.1002/jcp.30573
Alemi F, Raei Sadigh A, Malakoti F, Elhaei Y, Ghaffari SH, Maleki M, Asemi Z, Yousefi B, Targhazeh N, Majidinia M. Molecular mechanisms involved in DNA repair in human cancers: An overview of PI3k/Akt signaling and PIKKs crosstalk. J Cell Physiol. 2021 Sep 13; doi: 10.1002/jcp.30573. Epub 2021 Sep 13. PMID: 34515349.
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J Cell Physiol. 2021 Sep 13; doi: 10.1002/jcp.30573. Epub 2021 Sep 13.

Molecular mechanisms involved in DNA repair in human cancers: An overview of PI3k/Akt signaling and PIKKs crosstalk.

Journal of cellular physiology

Forough Alemi, Aydin Raei Sadigh, Faezeh Malakoti, Yusuf Elhaei, Seyed Hamed Ghaffari, Masomeh Maleki, Zatollah Asemi, Bahman Yousefi, Niloufar Targhazeh, Maryam Majidinia

Affiliations

  1. Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
  2. Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
  3. Department of Orthopedics, Shohada Medical Research & Training Hospital, Tabriz University of Medical Sciences, Tabriz, Iran.
  4. Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran.
  5. Solid Tumor Research Center, Urmia University of Medical Sciences, Urmia, Iran.

PMID: 34515349 DOI: 10.1002/jcp.30573

Abstract

The cellular genome is frequently subjected to abundant endogenous and exogenous factors that induce DNA damage. Most of the Phosphatidylinositol 3-kinase-related kinases (PIKKs) family members are activated in response to DNA damage and are the most important DNA damage response (DDR) proteins. The DDR system protects the cells against the wrecking effects of these genotoxicants and repairs the DNA damage caused by them. If the DNA damage is severe, such as when DNA is the goal of chemo-radiotherapy, the DDR drives cells toward cell cycle arrest and apoptosis. Some intracellular pathways, such as PI3K/Akt, which is overactivated in most cancers, could stimulate the DDR process and failure of chemo-radiotherapy with the increasing repair of damaged DNA. This signaling pathway induces DNA repair through the regulation of proteins that are involved in DDR like BRCA1, HMGB1, and P53. In this review, we will focus on the crosstalk of the PI3K/Akt and PIKKs involved in DDR and then discuss current achievements in the sensitization of cancer cells to chemo-radiotherapy by PI3K/Akt inhibitors.

© 2021 Wiley Periodicals LLC.

Keywords: DNA damage response; PI3K/Akt; malignancy; signaling pathway

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