CDT1 drives replication overlicensing and enhances tumorigenesis in the gut^†

Abstract

Colorectal carcinoma (CRC) is one of the most common forms of malignancy in the Western world. Recent decades have witnessed enormous progress in our understanding of the mechanisms that sustain CRC, even though the factors implicated in the initiation and progression of this neoplasia are not fully understood. A recent study published in The Journal of Pathology looked at the consequences of hyperactivity of chromatin licensing and DNA replication factor 1 (CDT1), a regulator of DNA replication that is produced in excess in CRC, on the course of intestinal tumorigenesis. Mice engineered to selectively overexpress CDT1 and/or lack Geminin, an inhibitor of CDT1, in the intestinal epithelium were more susceptible to experimental intestinal tumorigenesis compared to wild-type mice. This work supports the pro-tumorigenic role of CDT1 and suggests the potential prognostic value of this protein in CRC.

Transcriptome analysis suggests broad jejunal alterations in Linghu’s obesity-diarrhea syndrome: A pilot study

“…Our findings suggested down-regulation of genes associated with DNA replication in the jejunal mucosa of ODS patients, which may diminish intestinal regeneration and self-repair after damage. CDT1 , an essential component for the assembly of a pre-replicative complex[ 21 , 22 ], was down-regulated in these patients and network interaction analysis suggested that this gene plays a role in the development of ODS. A recent study reported an up-regulation of DNA replication licensing factors and robust acceleration of intestinal epithelial proliferation after glutamine (Gln) supplementation[ 23 ].…”