Please use this identifier to cite or link to this item: https://doi.org/10.26508/lsa.202101144
Title: Suppression of isoprenylcysteine carboxylmethyltransferase compromises DNA damage repair
Authors: Tang, Jingyi 
Casey, Patrick J. 
Wang, Mei 
Issue Date: 5-Oct-2021
Publisher: Rockefeller University Press
Citation: Tang, Jingyi, Casey, Patrick J., Wang, Mei (2021-10-05). Suppression of isoprenylcysteine carboxylmethyltransferase compromises DNA damage repair. Life Science Alliance 4 (12) : e202101144. ScholarBank@NUS Repository. https://doi.org/10.26508/lsa.202101144
Rights: Attribution 4.0 International
Abstract: DNA damage is a double-edged sword for cancer cells. On the one hand, DNA damage–induced genomic instability contributes to cancer development; on the other hand, accumulating damage compromises proliferation and survival of cancer cells. Understanding the key regulators of DNA damage repair machinery would benefit the development of cancer therapies that induce DNA damage and apoptosis. In this study, we found that isoprenylcysteine carboxylmethyltransferase (ICMT), a posttranslational modification enzyme, plays an important role in DNA damage repair. We found that ICMT suppression consistently reduces the activity of MAPK signaling, which compromises the expression of key proteins in the DNA damage repair machinery. The ensuing accumulation of DNA damage leads to cell cycle arrest and apoptosis in multiple breast cancer cells. Interestingly, these observations are more pronounced in cells grown under anchorage-independent conditions or grown in vivo. Consistent with the negative impact on DNA repair, ICMT inhibition transforms the cancer cells into a “BRCA-like” state, hence sensitizing cancer cells to the treatment of PARP inhibitor and other DNA damage–inducing agents. © 2021 Tang et al.
Source Title: Life Science Alliance
URI: https://scholarbank.nus.edu.sg/handle/10635/233636
ISSN: 2575-1077
DOI: 10.26508/lsa.202101144
Rights: Attribution 4.0 International
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