Chromosome fragility can lead to genome rearrangements, which are a hallmark of cancer, including breast cancer.Although DNA breaks can be induced by exogenous damage, it has remained largely unclear how normal cells encounter double strand breaks (DSBs) in the absence of DNA damaging agents.Recent evidence suggests that chromosomal breaks occur predominantly during S phase, due to the collapse of stalled replication forks.One factor that appears to be crucial to maintain stable replication forks is mini-chromosome maintenance protein (Mcm) 10.Mcm10 is essential in all eukaryotes and its central core domain is evolutionarily conserved.Mcm10 has been shown to link helicase and polymerization activities during lagging strand synthesis and is required to recruit DNA polymerase alpha to replication forks to initiate DNA synthesis.