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Ito, K. K.

Publications and source records attributed to Ito, K. K..

2 recordsLinked to original sources

Cep57 and Cep57L1 cooperatively maintain centriole engagement during interphase to ensure proper centriole duplication cycle

Centrioles duplicate in the interphase only once per cell cycle. Newly formed centrioles remain associated with their mother centrioles. The two centrioles disengage at the end of mitosis, which licenses centriole duplication in the next cell cycle. Therefore, timely centriole disengagement is critical for the proper centriole duplication cycle. However, the mechanisms underlying centriole engagement during interphase are poorly understood. Here, we show that Cep57 and Cep57L1 cooperatively maintain centriole engagement during interphase. Co-depletion of Cep57 and Cep57L1 induces precocious centriole disengagement in the interphase without compromising cell cycle progression. The disengaged daughter centrioles convert into centrosomes during interphase in a Plk1-dependent manner. Furthermore, the centrioles reduplicate and the centriole number increases, which results in chromosome segregation errors. Overall, these findings demonstrate that the maintenance of centriole engagement by Cep57 and Cep57L1 during interphase is crucial for the tight control of centriole copy number and thus for proper chromosome segregation.

cell biology

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.

cell biology