MCM3AP, a novel acetyltransferase that acetylates replication protein MCM3.
The MCM proteins are essential for the initiation of DNA replication. We have isolated an MCM3-associated protein (MCM3AP) in a two-hybrid screen using MCM3. Here we demonstrate that MCM3AP is an acetyltransferase which acetylates MCM3 and that chromatin-bound MCM3 is acetylated in vivo. The MCM3 acetylase, MCM3AP, is also chromatin-bound. This study also indicates that MCM3AP contains putative acetyl CoA binding motifs conserved within the GCN5-related N-acetyltransferase superfamily. Mutation of those motifs significantly inhibits the MCM3 acetylase activity. Over-expression of MCM3AP inhibits DNA replication, whereas mutation of the acetylase motifs abolishes this effect, suggesting that acetylation plays a role in DNA replication. Taken together, we suggest that MCM3 acetylation is a novel pathway which might regulate DNA replication.
Wellcome/CRC Institute, Cambridge, UK. yt215@cam.ac.uk
Y
Y
Takei
M
M
Swietlik
A
A
Tanoue
G
G
Tsujimoto
T
T
Kouzarides
R
R
Laskey
D000105:Acetyl Coenzyme A / Q000378:metabolism; D000107:Acetylation; D000123:Acetyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000494:pharmacology; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D017124:Conserved Sequence / Q000235:genetics; D004268:DNA-Binding Proteins; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008898:Mimosine / Q000494:pharmacology; D064126:Minichromosome Maintenance Complex Component 3; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D015739:Nocodazole / Q000494:pharmacology; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment
D000970:Antineoplastic Agents; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C066470:MCM3 protein, human; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; D008898:Mimosine; D000105:Acetyl Coenzyme A; D000123:Acetyltransferases; C406825:MCM3AP protein, human; D064126:Minichromosome Maintenance Complex Component 3; D015739:Nocodazole