Double-strand break (DSB) damage in yeast and mammalian cells induces the rapid ATM (ataxia telangiectasia mutated)/ATR (ataxia telangiectasia and Rad3 related)-dependent phosphorylation of histone H2AX (γ-H2AX). In budding yeast, a single endonuclease-induced DSB triggers γ-H2AX modification of 50 kb on either side of the DSB. The extent of γ-H2AX spreading does not depend on the chromosomal sequences. DNA resection after DSB formation causes the slow, progressive loss of γ-H2AX from single-stranded DNA and, after several hours, the Mec1 (ATR)-dependent spreading of γ-H2AX to more distant regions. Heterochromatic sequences are only weakly modified upon insertion of a 3-kb silent HMR locus into a γ-H2AX–covered region. The presence of heterochromatin does not stop the phosphorylation of chromatin more distant from the DSB. In mouse embryo fibroblasts, γ-H2AX distribution shows that γ-H2AX foci increase in size as chromatin becomes more accessible. In yeast, we see a high level of constitutive γ-H2AX in telomere regions in the absence of any exogenous DNA damage, suggesting that yeast chromosome ends are transiently detected as DSBs.

Peroxisomes are metabolic organelles involved in lipid metabolism and cellular redox balance. Peroxisomal function is central to fatty acid oxidation, ether phospholipid synthesis, bile acid synthesis, and reactive oxygen species homeostasis. Human disorders caused by genetic mutations in peroxisome genes have led to extensive studies on peroxisome biology. Peroxisomal defects are linked to metabolic dysregulation in diverse human diseases, such as neurodegeneration and age-related disorders, revealing the significance of peroxisome metabolism in human health. Cancer is a disease with metabolic aberrations. Despite the critical role of peroxisomes in cell metabolism, the functional eects of peroxisomes in cancer are not as well recognized as those of other metabolic organelles, such as mitochondria. In addition, the significance of peroxisomes in cancer is less appreciated than it is in degenerative diseases. In this review, I summarize the metabolic pathways in peroxisomes and the dysregulation of peroxisome metabolism in cancer. In addition, I discuss the potential of inactivating peroxisomes to target cancer metabolism, which may pave the way for more eective cancer treatment.