DNA replication fork speed acts as a pacer in cortical neurogenesis.

ABSTRACT: DNA replication fork speed, which controls the rate of genome duplication, has emerged as a key regulator of cellular plasticity. However, its role in neurogenesis remains unexplored. Mini-chromosome maintenance complex (MCMs)-binding protein (MCMBP) functions as a chaperone for newly synthesized MCMs, increasing chromatin coverage to restrain fork speed. We demonstrate that selectively deleting Mcmbp in neural progenitor radial glial cells (RGCs) accelerates fork speed, triggering DNA damage, micronuclei formation, and widespread apoptosis, which ultimately activates p53 and causes microcephaly. Unexpectedly, concurrent deletion of Trp53 and Mcmbp further increases fork speed, leading to extensive RGC detachment from the ventricular zone and acquisition of outer-RGC characteristics. Mecha

SUBMITTER: Wang J 

PROVIDER: S-EPMC12627098 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature