Causes and Consequences of Nuclear Envelope Rupture and DNA Damage in Micronuclei

Abstract

Micronuclei are small, aberrant nuclear compartments containing mis-segregated chromosomes or chromosomal fragments. During telophase, dysfunctional micronuclear envelope reassembly leaves the micronuclear envelope highly unstable and rupture-prone. Following rupture, micronuclei attempt to repair membrane gaps, but the process is typically unsuccessful and may promote the invasion of ER tubules into the interior of micronuclei. These abnormalities cause ruptured micronuclei to accumulate significant DNA damage in the form of both single-stranded DNA and double-stranded breaks. Because micronuclei are capable of promoting genome instability, it is essential to understand the sources of DNA damage and the mechanism through which it arises in these structures. In this review, I will explore the causes and consequences of micronuclear envelope rupture, beginning with the processes surrounding improper micronuclear envelope reassembly. I will then discuss micronuclear envelope rupture, attempted micronuclear envelope repair and its consequences, and the proposed causes of micronuclear DNA damage.