Deconstructing a Conserved Protein Family: The Role of MCM Proteins in Eukaryotic DNA Replication

2006 ◽  
pp. 129-155 ◽  
Author(s):  
Sally G. Pasion ◽  
Susan L. Forsburg
Keyword(s):  
Dna Replication ◽  
Protein Family ◽  
Eukaryotic Dna ◽  
Mcm Proteins

scholarly journals Essential Role of MCM Proteins in Premeiotic DNA Replication

2002 ◽  
Vol 13 (2) ◽  
pp. 435-444 ◽  
Author(s):  
Karola Lindner ◽  
Juraj Gregán ◽  
Stuart Montgomery ◽  
Stephen E. Kearsey
Keyword(s):  
Dna Replication ◽  
S Phase ◽  
Yeast Cells ◽  
Critical Event ◽  
Minichromosome Maintenance ◽  
Cell Cycles ◽  
Eukaryotic Dna ◽  
Mcm Proteins ◽  
Meiotic Cycle

A critical event in eukaryotic DNA replication involves association of minichromosome maintenance (MCM2–7) proteins with origins, to form prereplicative complexes (pre-RCs) that are competent for initiation. The ability of mutants defective in MCM2–7 function to complete meiosis had suggested that pre-RC components could be irrelevant to premeiotic S phase. We show here that MCM2–7 proteins bind to chromatin in fission yeast cells preparing for meiosis and during premeiotic S phase in a manner suggesting they in fact are required for DNA replication in the meiotic cycle. This is confirmed by analysis of a degron mcm4 mutant, which cannot carry out premeiotic DNA replication. Later in meiosis, Mcm4 chromatin association is blocked between meiotic nuclear divisions, presumably accounting for the absence of a second round of DNA replication. Together, these results emphasize similarity between replication mechanisms in mitotic and meiotic cell cycles.

Paradoxes of eukaryotic DNA replication: MCM proteins and the random completion problem

BioEssays ◽  
2003 ◽  
Vol 25 (2) ◽  
pp. 116-125 ◽  
Author(s):  
Olivier Hyrien ◽  
Kathrin Marheineke ◽  
Arach Goldar
Keyword(s):  
Dna Replication ◽  
Completion Problem ◽  
Eukaryotic Dna ◽  
Mcm Proteins

The physical interaction of Mcm10 with Cdc45 modulates their DNA-binding properties

2013 ◽  
Vol 454 (2) ◽  
pp. 333-343 ◽  
Author(s):  
Roberta Di Perna ◽  
Valentina Aria ◽  
Mariarosaria De Falco ◽  
Vincenzo Sannino ◽  
Andrei L. Okorokov ◽  
...  
Keyword(s):  
Dna Replication ◽  
Dna Binding ◽  
Replication Fork ◽  
Physical Interaction ◽  
Eukaryotic Dna ◽  
And Function ◽  
First Time ◽  
Dna Binding Properties

The eukaryotic DNA replication protein Mcm10 (mini-chromosome maintenance 10) associates with chromatin in early S-phase and is required for assembly and function of the replication fork protein machinery. Another essential component of the eukaryotic replication fork is Cdc45 (cell division cycle 45), which is required for both initiation and elongation of DNA replication. In the present study we characterize, for the first time, the physical and functional interactions of human Mcm10 and Cdc45. First we demonstrated that Mcm10 and Cdc45 interact in cell-free extracts. We then analysed the role of each of the Mcm10 domains: N-terminal, internal and C-terminal (NTD, ID and CTD respectively). We have detected a direct physical interaction between CTD and Cdc45 by both in vitro co-immunoprecipitation and surface plasmon resonance experiments. On the other hand, we have found that the interaction of the Mcm10 ID with Cdc45 takes place only in the presence of DNA. Furthermore, we found that the isolated ID and CTD domains are fully functional, retaining DNA-binding capability with a clear preference for bubble and fork structures, and that they both enhance Cdc45 DNA-binding affinity. The results of the present study demonstrate that human Mcm10 and Cdc45 directly interact and establish a mutual co-operation in DNA binding.

Methanococcus maripaludis: an archaeon with multiple functional MCM proteins?

2009 ◽  
Vol 37 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Alison D. Walters ◽  
James P.J. Chong
Keyword(s):  
Dna Replication ◽  
Biochemical Characterization ◽  
Model Organisms ◽  
Methanococcus Maripaludis ◽  
Replication Process ◽  
Archaeal Species ◽  
Wide Range ◽  
Eukaryotic Dna ◽  
Good Potential ◽  
Mcm Proteins

There are a large number of proteins involved in the control of eukaryotic DNA replication, which act together to ensure DNA is replicated only once every cell cycle. Key proteins involved in the initiation and elongation phases of DNA replication include the MCM (minchromosome maintenance) proteins, MCM2–MCM7, a family of six related proteins believed to act as the replicative helicase. Genome sequencing has revealed that the archaea possess a simplified set of eukaryotic replication homologues. The complexity of the DNA replication machinery in eukaryotes has led to a number of archaeal species being adapted as model organisms for the study of the DNA replication process. Most archaea sequenced to date possess a single MCM homologue that forms a hexameric complex. Recombinant MCMs from several archaea have been used in the biochemical characterization of the protein, revealing that the MCM complex has ATPase, DNA-binding and -unwinding activities. Unusually, the genome of the methanogenic archaeon Methanococcus maripaludis contains four MCM homologues, all of which contain the conserved motifs required for function. The availability of a wide range of genetic tools for the manipulation of M. maripaludis and the relative ease of growth of this organism in the laboratory makes it a good potential model for studying the role of multiple MCMs in DNA replication.

Role of nuclear architecture in the initiation of eukaryotic DNA replication

Biochimie ◽  
1997 ◽  
Vol 79 (9-10) ◽  
pp. 541-548 ◽  
Author(s):  
O. Hyrien ◽  
C. Maric ◽  
I. Lucas
Keyword(s):  
Dna Replication ◽  
Nuclear Architecture ◽  
Eukaryotic Dna

scholarly journals Biochemical Analysis of the Intrinsic Mcm4-Mcm6-Mcm7 DNA Helicase Activity

1999 ◽  
Vol 19 (12) ◽  
pp. 8003-8015 ◽  
Author(s):  
Zhiying You ◽  
Yuki Komamura ◽  
Yukio Ishimi
Keyword(s):  
Dna Replication ◽  
Dna Binding ◽  
Dna Helicase ◽  
Binding Activity ◽  
Helicase Activity ◽  
Single Stranded Dna ◽  
Dna Binding Activity ◽  
Eukaryotic Dna ◽  
Mcm Proteins ◽  
Biochemical Analyses

ABSTRACT Mcm proteins play an essential role in eukaryotic DNA replication, but their biochemical functions are poorly understood. Recently, we reported that a DNA helicase activity is associated with an Mcm4-Mcm6-Mcm7 (Mcm4,6,7) complex, suggesting that this complex is involved in the initiation of DNA replication as a DNA-unwinding enzyme. In this study, we have expressed and isolated the mouse Mcm2,4,6,7 proteins from insect cells and characterized various mutant Mcm4,6,7 complexes in which the conserved ATPase motifs of the Mcm4 and Mcm6 proteins were mutated. The activities associated with such preparations demonstrated that the DNA helicase activity is intrinsically associated with the Mcm4,6,7 complex. Biochemical analyses of these mutant Mcm4,6,7 complexes indicated that the ATP binding activity of the Mcm6 protein in the complex is critical for DNA helicase activity and that the Mcm4 protein may play a role in the single-stranded DNA binding activity of the complex. The results also indicated that the two activities of DNA helicase and single-stranded DNA binding can be separated.

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