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PMID:23449222
| Citation |
Fatoba, ST, Tognetti, S, Berto, M, Leo, E, Mulvey, CM, Godovac-Zimmermann, J, Pommier, Y and Okorokov, AL (2013) Human SIRT1 regulates DNA binding and stability of the Mcm10 DNA replication factor via deacetylation. Nucleic Acids Res. 41:4065-79 |
|---|---|
| Abstract |
The eukaryotic DNA replication initiation factor Mcm10 is essential for both replisome assembly and function. Human Mcm10 has two DNA-binding domains, the conserved internal domain (ID) and the C-terminal domain (CTD), which is specific to metazoans. SIRT1 is a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase that belongs to the sirtuin family. It is conserved from yeast to human and participates in cellular controls of metabolism, longevity, gene expression and genomic stability. Here we report that human Mcm10 is an acetylated protein regulated by SIRT1, which binds and deacetylates Mcm10 both in vivo and in vitro, and modulates Mcm10 stability and ability to bind DNA. Mcm10 and SIRT1 appear to act synergistically for DNA replication fork initiation. Furthermore, we show that the two DNA-binding domains of Mcm10 are modulated in distinct fashion by acetylation/deacetylation, suggesting an integrated regulation mechanism. Overall, our study highlights the importance of protein acetylation for DNA replication initiation and progression, and suggests that SIRT1 may mediate a crosstalk between cellular circuits controlling metabolism and DNA synthesis. |
| Links |
PubMed PMC3627603 Online version:10.1093/nar/gkt131 |
| Keywords |
Acetylation; Cell Cycle; Cell Cycle Proteins/chemistry; Cell Cycle Proteins/metabolism; Cell Line; Chromatin/metabolism; DNA Replication; Humans; Protein Binding; Protein Interaction Domains and Motifs; Protein Stability; Replication Origin; Sirtuin 1/antagonists & inhibitors; Sirtuin 1/metabolism |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0017136: NAD-dependent histone deacetylase activity |
ECO:0000314: |
F |
Figure 1 |
complete | ||||
See also
References
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