Anti-MCM6 monoclonal antibody, clone 8E9

Variation at the FADS1/FADS2 gene cluster is functionally associated with differences in lipid metabolism and is often hypothesized to reflect adaptation to an agricultural diet. Here, we test the evidence for this relationship using both modern and ancient DNA data. We show that almost all the inhabitants of Europe carried the ancestral allele until the derived allele was introduced similar to 8,500 years ago by Early Neolithic farming populations. However, we also show that it was not under strong selection in these populations. We find that this allele, and other proposed agricultural adaptations at LCT/MCM6 and SLC22A4, were not strongly selected until much later, perhaps as late as the Bronze Age. Similarly, increased copy number variation at the salivary amylase gene AMY1 is not linked to the development of agriculture although, in this case, the putative adaptation precedes the agricultural transition. Our analysis shows that selection at the FADS locus was not tightly linked to the initial introduction of agriculture and the Neolithic transition. Further, it suggests that the strongest signals of recent human adaptation in Europe did not coincide with the Neolithic transition but with more recent changes in environment, diet, or efficiency of selection due to increases in effective population size.

Cyclin-dependent kinase 5 regulatory subunit-associated protein 3 (CDK5RAP3) was identified as a tumor suppressor in gastric cancer, while, minichromosome maintenance complex component 6 (MCM6), which is closely related to the initiation of DNA replication, was reported to be upregulated in multiple malignancies. However, the interaction between these two proteins has not been investigated in gastric cancer. Here, we evaluate the connection between CDK5RAP3 and MCM6 using mass spectrometry and immunoprecipitation. In cells, cell growth and invasiveness indicate that CDK5RAP3 acts as a tumor suppressor by preventing the effects of MCM6. The potential mechanism was revealed using immunofluorescence and nuclear protein extraction. In patients, immunohistochemistry and immunofluorescence show that the protein levels of CDK5RAP3 were markedly decreased in most gastric tumor tissues compared with adjacent nontumor tissues, and the expression levels of MCM6 in the nucleus showed the opposite trend. Prognostic analysis showed that the combined expression of CDK5RAP3 and MCM6 was an independent prognostic factor correlating with the overall survival of gastric cancer patients. Cox regression analysis indicated that the expression of CDK5RAP3 and MCM6 corresponded to T, N, and M stages. Our results demonstrate that CDK5RAP3 can interact with MCM6 and prevent MCM6 from translocating into the nucleus, which may be a potential mechanism through which CDK5RAP3 negatively regulates the proliferation of gastric cancer.