Human SIRT1 regulates DNA binding and stability of the Mcm10 DNA replication factor via deacetylation
Language: 
English
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.

Author(s): 
Fatoba, Samuel T.
Tognetti, Silvia
Berto, Melissa
Leo, Elisabetta
Mulvey, Claire M.
Godovac-Zimmermann, Jasminka
Pommier, Yves
Okorokov, Andrei L.
Item Type: 
Journal Article
Publication Title: 
Nucleic Acids Research
Journal Abbreviation: 
Nucleic Acids Res.
Publication Date: 
2013-04
Publication Year: 
2013
Pages: 
4065-4079
Volume: 
41
Issue: 
7
ISSN: 
1362-4962
DOI: 
10.1093/nar/gkt131
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 23449222 PMCID: PMC3627603

Turabian/Chicago Citation

Samuel T. Fatoba, Silvia Tognetti, Melissa Berto, Elisabetta Leo, Claire M. Mulvey, Jasminka Godovac-Zimmermann, Yves Pommier and Andrei L. Okorokov. 2013-04. "Human SIRT1 regulates DNA binding and stability of the Mcm10 DNA replication factor via deacetylation." Nucleic Acids Research 41: 7: 4065-4079. 10.1093/nar/gkt131.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1093/nar/gkt131 | issn = 1362-4962 | volume = 41 | pages = 4065-4079 | last = Fatoba | first = Samuel T. | coauthors = Tognetti, Silvia, Berto, Melissa, Leo, Elisabetta, Mulvey, Claire M., Godovac-Zimmermann, Jasminka, Pommier, Yves, Okorokov, Andrei L. | title = Human SIRT1 regulates DNA binding and stability of the Mcm10 DNA replication factor via deacetylation | journal = Nucleic Acids Research | date = 2013-04 | pmid = | pmc = }} </ref>