Sgo1 as a “guardian spirit” for preventing colon tumorigenesis

Micronuclei are small membrane-enclosed cytoplasmic bodies containing whole or fragmented chromosomes, which are formed during anaphase in aberrant mitosis and in response to genotoxic stress. in the latter scenario, the formation of micronuclei can be used to assess the toxicity of various chemicals and drugs. A report by Rello-varona et al. in a previous issue describes the elimination of micronuclei by autophagy. 1 Macroautophagy (hereafter referred to as autophagy) is a highly regulated cellular mechanism for degradation and recycling of cytoplasmic contents. This process begins with the formation of an autophagosome, a double membrane structure that engulfs parts of the cytosol and whole organelles, finally fusing with a lysosome to allow the degradation of the enclosed material. The final products, including amino acids, lipids and nucleotides, are released into the cyto-sol via permeases present at the lysosomal membrane and can then be used for ana-bolic reactions to maintain cellular functions. Autophagy is conserved from yeast to human and is regulated by the Atg family of proteins. 2 Autophagy is a general response to cellular stress, which mediates the clearance of dangerous cell components, such as damaged mitochondria, and intracellular pathogens, such as viral particles and bacteria. 3 The study by Rello-varona and colleagues demonstrates that micronuclei generated after cell cycle perturbations are surrounded by LC3-and p62-positive staining (Fig. 1). This phenomenon appears to be dependent on the autophagy regulators Atg7 and Atg5, as it is not observed in cells treated with siRnAs for Atg5 and Atg7. importantly, these micro-nuclei contain a reduced quantity of DnA, as determined by DnA binding dyes and fluorescent histone tagging, and exhibit a discon-tinuous membrane, suggesting that both the nuclear membrane and DnA are degraded by autophagy. As expected, these structures were also positive for the lysosomal marker Lamp2. interestingly, only micronuclei presenting symptoms of DnA damage were targeted, as indicated by labeling with phospho-γH2AX, a marker of DnA damage. 1 selective autophagy of organelles (e.g., mitochondria) and intracellular pathogens requires the recognition of LC3-interacting regions in target proteins at the surface of organelles and intracellular bacteria. 4 interestingly, Rello et al. report that micro-nuclei were also positive for p62, an LC3-interacting protein, 5 whereas no p62 staining was detected in LC3-negative micronuclei. it remains to be determined whether p62 represents the bona fide receptor for this new form of selective autophagy or micronucle-ophagy. Moreover, further studies are required to determine how DnA damage promotes …