Diverse genetic alteration dysregulates neuropeptide and intracellular signalling in the suprachiasmatic nuclei.

In mammals, intrinsic 24 h or circadian rhythms are primarily generated by the suprachiasmatic nuclei (SCN). Rhythmic daily changes in the transcriptome and proteome of SCN cells are controlled by interlocking transcription-translation feedback loops (TTFLs) of core clock genes and their proteins. SCN cells function as autonomous circadian oscillators, which synchronize through intercellular neuropeptide signalling.

Heterozygosity for p53 promotes microsatellite instability and tumorigenesis on a Msh2 deficient background.

In colorectal tumorigenesis, loss of function of the mismatch repair genes is closely associated with genomic instability at the nucleotide level whereas p53 deficiency has been linked with gross chromosomal instability. We have addressed the contribution of these two forms of genetic instability to tumorigenesis using mice mutant for Msh2 and p53. As previously reported, deficiency of both genes leads to rapid lymphomagenesis Here we show that heterozygosity for p53 also markedly reduces survival on an Msh2 null background.