<i>CRY2</i> missense mutations suppress P53 and enhance cell growth
Alanna B. Chan, Gian Carlo G. Parico, Jennifer L. Fribourgh, Lara Ibrahim, Michael J. Bollong, Carrie L. Partch, Katja Lamia
Abstract
Significance Disruption of circadian rhythms enhances cancer risk, but the underlying mechanisms are largely unknown. The circadian repressors CRY1 and CRY2 evolved from light-activated DNA-repair enzymes, suggesting that they may be involved. Here, we demonstrate that missense mutations in CRY2 reported in The Cancer Genome Atlas suppress P53 target-gene expression and enhance the growth of MYC-transformed fibroblasts. Our identification of point mutations in CRY2 in human tumors that influence P53 activity and cell growth provides evidence for a clinically relevant molecular connection between CRYs and P53. Furthermore, these mutants will enable new strategies to investigate underlying molecular mechanisms and inform a growing effort to identify selective chemical modulators of CRY1 and/or CRY2.