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MCMBP promotes the assembly of the MCM2–7 hetero-hexamer to ensure robust DNA replication in human cells
by
Santosa, Venny
, Ishiguro, Kei-ichiro
, Saito, Yuichiro
, Kanemaki, Masato T
in
Adaptor Proteins, Signal Transducing - metabolism
/ Carrier Proteins - metabolism
/ Cell Biology
/ Cell Cycle Proteins - metabolism
/ Cells
/ Chromosomes and Gene Expression
/ DNA
/ DNA Damage
/ DNA Replication
/ genome instability
/ Genomes
/ Humans
/ MCM2–7
/ MCMBP
/ Minichromosome Maintenance Complex Component 2 - genetics
/ Minichromosome Maintenance Complex Component 2 - metabolism
/ Minichromosome Maintenance Proteins - metabolism
/ Nuclear Proteins - metabolism
/ Protein binding
/ protein complex assembly
/ Tumor proteins
/ Tumor Suppressor Protein p53 - genetics
2022
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MCMBP promotes the assembly of the MCM2–7 hetero-hexamer to ensure robust DNA replication in human cells
by
Santosa, Venny
, Ishiguro, Kei-ichiro
, Saito, Yuichiro
, Kanemaki, Masato T
in
Adaptor Proteins, Signal Transducing - metabolism
/ Carrier Proteins - metabolism
/ Cell Biology
/ Cell Cycle Proteins - metabolism
/ Cells
/ Chromosomes and Gene Expression
/ DNA
/ DNA Damage
/ DNA Replication
/ genome instability
/ Genomes
/ Humans
/ MCM2–7
/ MCMBP
/ Minichromosome Maintenance Complex Component 2 - genetics
/ Minichromosome Maintenance Complex Component 2 - metabolism
/ Minichromosome Maintenance Proteins - metabolism
/ Nuclear Proteins - metabolism
/ Protein binding
/ protein complex assembly
/ Tumor proteins
/ Tumor Suppressor Protein p53 - genetics
2022
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MCMBP promotes the assembly of the MCM2–7 hetero-hexamer to ensure robust DNA replication in human cells
by
Santosa, Venny
, Ishiguro, Kei-ichiro
, Saito, Yuichiro
, Kanemaki, Masato T
in
Adaptor Proteins, Signal Transducing - metabolism
/ Carrier Proteins - metabolism
/ Cell Biology
/ Cell Cycle Proteins - metabolism
/ Cells
/ Chromosomes and Gene Expression
/ DNA
/ DNA Damage
/ DNA Replication
/ genome instability
/ Genomes
/ Humans
/ MCM2–7
/ MCMBP
/ Minichromosome Maintenance Complex Component 2 - genetics
/ Minichromosome Maintenance Complex Component 2 - metabolism
/ Minichromosome Maintenance Proteins - metabolism
/ Nuclear Proteins - metabolism
/ Protein binding
/ protein complex assembly
/ Tumor proteins
/ Tumor Suppressor Protein p53 - genetics
2022
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MCMBP promotes the assembly of the MCM2–7 hetero-hexamer to ensure robust DNA replication in human cells
Journal Article
MCMBP promotes the assembly of the MCM2–7 hetero-hexamer to ensure robust DNA replication in human cells
2022
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Overview
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.
Publisher
eLife Science Publications, Ltd,eLife Sciences Publications, Ltd,eLife Sciences Publications Ltd
Subject
Adaptor Proteins, Signal Transducing - metabolism
/ Carrier Proteins - metabolism
/ Cell Cycle Proteins - metabolism
/ Cells
/ Chromosomes and Gene Expression
/ DNA
/ Genomes
/ Humans
/ MCM2–7
/ MCMBP
/ Minichromosome Maintenance Complex Component 2 - genetics
/ Minichromosome Maintenance Complex Component 2 - metabolism
/ Minichromosome Maintenance Proteins - metabolism
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