DNA Damage Response Protein CHK2 Regulates Metabolism in Liver Cancer

Defective mitosis with chromosome missegregation can have a dramatic effect on genome integrity by causing DNA damage, activation of the DNA damage response (DDR), and chromosomal instability. Although this is an energy-dependent process, mechanisms linking DDR to cellular metabolism are unknown. Here we show that checkpoint kinase 2 (CHK2), a central effector of DDR, regulates cellular energy production by affecting glycolysis and mitochondrial functions. Patients with hepatocellular carcinoma (HCC) had increased CHK2 mRNA in blood, which was associated with elevated tricarboxylic acid cycle (TCA) metabolites. CHK2 controlled expression of succinate dehydrogenase (SDH) and intervened with mitochondrial functions. DNA damage and CHK2 promoted SDH activity marked by increased succinate oxidation through the TCA cycle; this was confirmed in a transgenic model of HCC with elevated DNA damage. Mitochondrial analysis identified CHK2-controlled expression of SDH as key in sustaining reactive oxygen species production. Cells with DNA damage and elevated CHK2 relied significantly on glycolysis for ATP production due to dysfunctional mitochondria, which was abolished by CHK2 knockdown. This represents a vulnerability created by the DNA damage response that could be exploited for development of new therapies

Characterization of seed oil components from Nephelium lappaceum L

The chemical composition of the oil extracted from the seeds of Nephelium lappaceum L., commonly known as rambutan, has been investigated. The oil from this plant, similar to other members of the Sapindaceae, typically contained triglycerides (83%) and cyanolipids (17%). The latter consisted of type III cyanolipids, 1-cyano-2-hydroxymethylprop-1-en-3-ol diesters. Structural investigation of the oil components was carried out using chemical, chromatographic and spectroscopic methods. Oleic and arachidic acids were the two dominant esterified fatty acyl chains in both triglycerides and cyanolipids. Eicosenoic acids (cis-vaccenic and paullinic acid) were present in higher amounts in the cyanolipid fraction of the oil