SUMMARY DNA fork speed, the rate of replication fork progression, has emerged as a cellular plasticity regulator, however, for its role in neurogenesis has never been explored before. Here, we show that fork speed was increased as neural progenitors-radial glial cells (RGCs) transition from symmetric to asymmetric divisions. After selectively deleting mini-chromosome maintenance complex (MCMs)-binding protein (MCMBP), fork speed was increased in RGCs, resulted in widespread apoptosis, DNA damage and micronuclei at later stage of neurogenesis, which triggered p53 activation and led to microcephaly. Further, co-deletion of Trp53 with Mcmbp largely rescued brain phenotype, however, fork speed became faster, unexpectedly resulting in massive RGCs detachment from their resident place. Mechanistically, MCM3 can interact with p53 mediating centrosome biogenesis to anchor RGCs during DNA replication. Finally, behavior analysis indicated that fast fork speed led to an anxiety-like behavior in mice. Altogether, our results illuminate an unrecognized role about DNA fork speed in corticogenesis.
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