The "Mutated in Colorectal Cancer" Protein Is a Novel Target of the UV-Induced DNA Damage Checkpoint

Laurent Pangon (Lead / Corresponding author), Nicholas D. Sigglekow, Mark Larance, Sam Al-Sohaily, Dessislava N. Mladenova, Christina I. Selinger, Elizabeth A. Musgrove, Maija R. J. Kohonen-Corish

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    13 Citations (Scopus)

    Abstract

    MCC is a potential tumor suppressor gene, which is silenced by promoter hypermethylation in a subset of colorectal cancers. However, its functions have remained poorly understood. In the present study, we describe a novel function of MCC in the DNA damage response. Several novel phosphorylation sites were identified by mass spectrometry, including 2 highly conserved ATM/ATR consensus sites at serine 118 and serine 120. In addition, exposure to ultraviolet radiation (UV), but not phleomycin, caused PI3K-dependent phosphorylation of MCC and its nuclear localization. Re-expression of MCC in HCT15 colorectal cancer cells led to a G2/M arrest, and MCC knockdown impaired the induction of a G2/M arrest following UV radiation. Finally, mutation of S118/120 to alanine did not affect MCC nuclear shuttling following UV but did impair MCC G2/M checkpoint activity. Thus, these results suggest that MCC is a novel target of the DNA damage checkpoint and that MCC is required for the complete cell cycle arrest in the G2/M phase in response to UV.
    Original languageEnglish
    Pages (from-to)917-926
    Number of pages10
    JournalGenes and Cancer
    Volume1
    Issue number9
    DOIs
    Publication statusPublished - Sep 2010

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  • Cite this

    Pangon, L., Sigglekow, N. D., Larance, M., Al-Sohaily, S., Mladenova, D. N., Selinger, C. I., Musgrove, E. A., & Kohonen-Corish, M. R. J. (2010). The "Mutated in Colorectal Cancer" Protein Is a Novel Target of the UV-Induced DNA Damage Checkpoint. Genes and Cancer, 1(9), 917-926. https://doi.org/10.1177/1947601910388937