Figure 6.

Extensive DNA damage of chromosomes in micronuclei (MN). Micronuclei can form by missegregation of whole chromosomes after mitotic errors. Pictured here is a “merotelic” kinetochore attachment where a single intact chromatid is caught in a tug-of-war between microtubules from opposite poles. Micronuclei can also originate from chromosome breaks, generating acentric chromosome fragments, or be generated from chromosome bridges by a mechanism that has not been determined (Hoffelder et al. 2004). (Left) Newly generated micronuclei can undergo irreversible loss of nuclear membrane integrity (Hatch et al. 2013). If this occurs during S phase, chromosomes in micronuclei will acquire massive DNA damage. (Right) Alternatively, late-replicating chromosomes in micronuclei may undergo DNA damage if the cell enters mitosis before micronuclear replication is complete (Crasta et al. 2012), subjecting the chromosome to premature chromosome compaction (PCC). The extent and mechanism of DNA damage during PCC remains to be established. During the subsequent cell division cycle, the micronuclear genome can be reincorporated into the primary nucleus, remain isolated in a micronucleus, or possibly be lost due to autophagy or extrusion.