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

By Yuichiro Saito, Venny Santosa, K. Ishiguro, Masato T. Kanemaki. 2022

14 citations recorded by the source corpus.

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.

Subfields: Molecular Biology, Oncology

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In Molecular Biology

  1. Johannes C. Walter
  2. Masato T. Kanemaki
  3. Sachiko Muramatsu

In Oncology

  1. Masato T. Kanemaki

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