Small spaces, big problems: The abnormal nucleoplasm of micronuclei and its consequences

Abstract

Micronuclei (MN) form from missegregated chromatin that recruits its own nuclear envelope during mitotic exit and are a common consequence of chromosomal instability. MN are unstable due to errors in nuclear envelope organization and frequently rupture, leading to loss of compartmentalization, loss of nuclear functions, and major changes in genome stability and gene expression. However, recent work found that, even prior to rupture, nuclear processes can be severely defective in MN, which may contribute to rupture-associated defects and have lasting consequences for chromatin structure and function. In this review we discuss work that highlights nuclear function defects in intact MN, including their mechanisms and consequences, and how biases in chromosome missegregation into MN may affect the penetrance of these defects. Illuminating the nuclear environment of MN demonstrates that MN formation alone has major consequences for both the genome and cell and provides new insight into how nuclear content is regulated.