Small but mighty: the causes and consequences of micronucleus rupture

Abstract

Micronuclei are small DNA-containing nuclear structures that are spatially isolated from the main nucleus. They are frequently found in pathologies, including cancer. It was recently shown that these nuclear structures are not only biomarkers of disease but also play an active role in tumor biology. Many consequences of micronucleus formation on tumor biology are dependent on the frequent and irreversible rupture of their nuclear envelopes, which results in the exposure of their DNA contents to the cytoplasm. In this review, we discuss models of defective nuclear envelope deposition on missegregated chromosomes that lead to nuclear envelope rupture. Furthermore, we expound upon the various downstream consequences of micronucleus nuclear envelope rupture on cells. These consequences include a massive DNA rearrangement phenomenon called chromothripsis and activation of the cGAS-STING innate immune signaling pathway, which can be a double-edged sword with tumorigenesis and tumor prevention functions. Although micronuclei are small structures, the impact they have on cells and their microenvironment is quite large. Cancer: Rupture of micronuclei drives genome instability Micronuclei, which contain faulty chromosomes or chromosome fragments and occur outside the main cellular nucleus, are prone to rupturing, which leads to DNA changes that can drive tumor development. A team led by Mijung Kwon from Ewha Womans University in Seoul and Jae-Ho Lee of Ajou University School of Medicine in Suwon, both in South Korea, review how these micronuclei tend to burst, spilling their contents into the cell with devastating consequences. The chromosomes they contain break into tiny fragments and this broken DNA finds its way into the main nucleus, leading to chromosomal rearrangements that can permanently alter genomic function. The rupture of micronuclei also activates a part of the innate immune system that can promote cancer cell invasion and spread. Drugs targeting these processes could aid in the treatment of cancer.