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bioRxiv · 10.1101/2022.02.08.479529

MCMBP promotes the assembly of the MCM2-7 hetero-hexamer to ensure robust DNA replication in human cells

Saito, Y.·Santosa, V.·Ishiguro, K.-i.·Kanemaki, M. T.
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Abstract

The MCM2-7 hetero-hexamer is the replicative DNA helicase that plays a central role in eukaryotic DNA replication. In proliferating cells, the expression level of the MCM2-7 hexamer is kept high, which safeguards the integrity of the genome. However, how the MCM2-7 hexamer is assembled in living cells remains unknown. Here, we revealed that the MCM-binding protein (MCMBP) plays a critical role in the assembly of this hexamer in human cells. MCMBP associates with MCM3 which is essential for maintaining the level of the MCM2-7 hexamer. Acute depletion of MCMBP demonstrated that it contributes to MCM2-7 assembly using nascent MCM3. Cells depleted of MCMBP gradually ceased to proliferate because of reduced replication licensing. Under this condition, p53-positive cells exhibited arrest in the G1 phase, whereas p53-null cells entered the S phase and lost their viability because of the accumulation of DNA damage, suggesting that MCMBP is a potential target for killing p53-deficient cancers.

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Saito, Y., Santosa, V., Ishiguro, K.-i., Kanemaki, M. T.. 2022-02-08. MCMBP promotes the assembly of the MCM2-7 hetero-hexamer to ensure robust DNA replication in human cells. https://doi.org/10.1101/2022.02.08.479529

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