DONSON, a gene responsible for microcephalic primordial dwarfism, ensures proper centriole duplication cycle by maintaining centriole engagement during interphase

Microcephalic primordial dwarfism (MPD) is a genetic disorder characterized by short stature and microcephaly. MPD-related genes are known to regulate centrosome biogenesis, DNA replication or the DNA damage response. Although some of the MPD-related proteins that are implicated in DNA replication localize to centrosomes, how these proteins affect centrosome biogenesis remains mostly elusive. Here, we revisit the potential function of these DNA replication mediators in human centrosome biogenesis. Among these proteins, depletion of DONSON leads to excessive number of centrosomes in interphase, caused by precocious centriole disengagement. Such disengaged centrioles are converted to centrosomes, followed by centriole reduplication during interphase. These extra centrosomes lead to abnormal spindle formation and chromosome segregation errors. Importantly, similar defects are observed in MPD patients’ cells with DONSON mutations, suggesting a possible cause of the disease. Overall, these results indicate that DONSON is involved in regulating the centriole duplication cycle by ensuring the maintenance of centriole engagement during interphase.