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The 'Mutated in Colorectal Cancer' protein is a novel target of the UV-induced DNA damage checkpoint.


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.

ISBN 1947-6019
Authors Pangon, L.; Sigglekow, N.D.; Larance, M.; Al-Sohaily, S.; Mladenova, D.N.; Selinger, C.I.; Musgrove, E.A.; Kohonen-Corish, M.
Responsible Garvan Author A/Prof Maija Kohonen-Corish
Publisher Name Genes & Cancer
Published Date 2010-06-01
Published Volume 1
Published Issue 9
Published Pages 917
Status Published in-print
URL link to publisher's version 10.1177/1947601910388937
OpenAccess link to author's accepted manuscript version