What is the significance of efficient assembly of the hexameric MCM2–7 helicase for DNA replication?
–A new hypothesis explaining the licensing checkpoint–

The assembly of the MCM2–7 hetero-hexamer and its significance in DNA replication.

Yuki Hatoyama and Masato T. Kanemaki.

Biochemical Society Transactions 2023 May 5 DOI:10.1042/BST20221465

To proliferate, cells must replicate chromosomal DNA, which encodes the genetic information. MCM2–7, the replication helicase that unwinds a double-strand DNA to generate a single-strand DNA, is essential for chromosomal DNA replication. The replicative MCM2–7 helicase forms a ring-shaped hexamer.

This review paper was published in Biochemical Society Transactions, a review journal published by the Biochemical Society. The review discusses how the MCM2–7 hexamer is efficiently assembled in cells and its physiological significance based on our recent report. In this review, we proposed a model in which MCMBP functions as a chaperone to promote the assembly of the MCM2–7 hexamer, resulting in the supply of sufficient amounts of MCM2–7 before DNA replication (Figure).

The existence of the licensing checkpoint was proposed, whereby the cell senses a lack of chromatin-bound MCM2–7 and arrests the cell cycle in the G1 phase. In this review, we proposed a new hypothesis that cells do not sense the amount of MCM2–7 directly. Instead, the cells with reduced MCM2–7 expression have DNA damage during DNA replication in the previous cell cycle, and they arrest the cell cycle by detecting this DNA damage in the next G1 phase.


Figure: A schematic diagram of the assembling the MCM2–7 hexameric complex.

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