to block cytokinesis to produce a binucleated cells. Acentric chromosome fragments may arise in a variety of ways. One way is that disrepair of DNA double-strand breaks can lead to symmetrical or asymmetrical chromatid and chromosome exchanges as well as chromatid and chromosome fragments. If DNA damage exceeds the repair capacity of the cell, unrepaired double-stranded DNA breaks may also result in acentric chromosome fragments. Another way eccentric chromosome fragments may arise is when defects in genes related to homologous recombinational repair (ex: ATM, BRCA1, BRCA2, and RAD51) result in a dysfunctional error-free homologous recombinational DNA repair pathway and causes the cell to resort to the error-prone non-homologous end-joining (NHEJ) repair pathway, increasing the likelihood of incorrect repair of DNA breaks, formation of dicentric chromosomes, and acentric chromosome fragments. If enzymes in the NHEJ repair pathway are defective as well, DNA breaks may not be repaired at all. Additionally, simultaneous excision repair of damaged or inappropriate bases incorporated in DNA that are in proximity and on opposite complementary DNA strands may lead to DNA double-stranded breaks and micronucleus formation, especially if the gap-filling step of the repair pathway is not completed. Micronuclei can also form from fragmented chromosomes when nucleoplasmic bridges (NPB) are formed, stretched, and broken during telophase. Micronuclei formation may also result from chromosome malsegregation during anaphase. Hypomethylation of cytosine in centromeric and pericentromeric areas and higher-order repeats of satellite DNA in centromeric DNA can result in such chromosomal loss events. Classical satellite DNA is normally heavily methylated at cytosine residues but may become almost fully unmethylated due to ICF syndrome (Immunodeficiency, centromere instability, and facial anomalies syndrome) or after treatment by DNA methyl transferase inhibitors. Since assembly of kinetochore proteins at centromeres is affected by the methylation of cytosine and histone proteins, a reduction in heterochromatin integrity as a result of hypomethylation can interfere with microtubule attachment to chromosomes and with the sensing of tension from correct microtubule-kinetochore connections. Other possible causes of chromosome loss that could lead to micronuclei formation are defects in kinetochore and microtubule interactions, defects in mitotic spindle assembly, mitosis check point defects, abnormal centrosome amplification, and telomeric end fusions that result in dicentric chromosomes that detach from the spindle during anaphase. Micronuclei originating from chromosome loss events and acentric chromosome fragments can be distinguished using pancentromeric DNA probes. Identification The number of micronuclei per cell can be predicted using the following formula: