Abstract
Chromoanasynthesis has been described as a novel cause of massive constitutional chromosomal rearrangements. Based on DNA replication machinery defects, chromoanasynthesis is characterized by the presence of chromosomal duplications and triplications locally clustered on one single chromosome, or a few chromosomes, associated with various other types of structural rearrangements. Two distinct mechanisms have been described for the formation of these chaotic genomic disorders, i.e. the fork stalling and template switching and the microhomology-mediated break-induced replication. Micronucleus-based processes have been evidenced as a causative mechanism, thus, highlighting the close connection between segregation errors and structural rearrangements. Accumulating data indicate that chromoanasynthesis is operating in human germline cells and during early embryonic development. The development of new tools for quantifying chromoanasynthesis events should provide further insight into the impact of this catastrophic cellular phenomenon in human reproduction.