Nonrepair functions of DNA mismatch repair proteins: new avenues for precision oncology.

DNA damage repair (DDR) proteins are well recognized as guardians of the genome that are frequently lost during malignant transformation of normal cells across cancer types. To date, their tumor suppressor functions have been generally regarded as a consequence of their roles in maintaining genomic stability: more genomic instability increases the risk of oncogenic transformation events. However, recent discoveries centering around DNA mismatch repair (MMR) proteins suggest a broader impact of the loss of DDR proteins on cellular processes beyond genomic instability.

Inflammatory Cytokines Rewire the Proinsulin Interaction Network in Human Islets.

Context: Aberrant biosynthesis and secretion of the insulin precursor proinsulin occurs in both type I and type II diabetes. Inflammatory cytokines are implicated in pancreatic islet stress and dysfunction in both forms of diabetes, but the mechanisms remain unclear.

Objective: We sought to determine the effect of the diabetes-associated cytokines on proinsulin folding, trafficking, secretion, and β-cell function.