How is the archaeal MCM helicase assembled at the origin? Possible mechanisms

2009 ◽  
Vol 37 (1) ◽  
pp. 7-11 ◽  
Author(s):  
Nozomi Sakakibara ◽  
Lori M. Kelman ◽  
Zvi Kelman
Keyword(s):  
Replication Fork ◽  
Biochemical Properties ◽  
Duplex Dna ◽  
Origin Of Replication ◽  
Minichromosome Maintenance ◽  
Replicative Helicase ◽  
Loading Process ◽  
Mcm Helicase

In order for any organism to replicate its DNA, a helicase must unwind the duplex DNA in front of the replication fork. In archaea, the replicative helicase is the MCM (minichromosome maintenance) helicase. Although much is known about the biochemical properties of the MCM helicase, the mechanism of assembly at the origin of replication is unknown. In the present paper, several possible mechanisms for the loading process are described.

scholarly journals Unwinding 20 Years of the Archaeal Minichromosome Maintenance Helicase

2020 ◽  
Vol 202 (6) ◽  
Author(s):  
Lori M. Kelman ◽  
William B. O’Dell ◽  
Zvi Kelman
Keyword(s):  
Dna Replication ◽  
Replication Fork ◽  
Duplex Dna ◽  
Chromosomal Dna ◽  
Minichromosome Maintenance ◽  
Replicative Helicase ◽  
Dna Helicases ◽  
First Report ◽  
20Th Anniversary

ABSTRACT Replicative DNA helicases are essential cellular enzymes that unwind duplex DNA in front of the replication fork during chromosomal DNA replication. Replicative helicases were discovered, beginning in the 1970s, in bacteria, bacteriophages, viruses, and eukarya, and, in the mid-1990s, in archaea. This year marks the 20th anniversary of the first report on the archaeal replicative helicase, the minichromosome maintenance (MCM) protein. This minireview summarizes 2 decades of work on the archaeal MCM.

Structure and function of the GINS complex, a key component of the eukaryotic replisome

2010 ◽  
Vol 425 (3) ◽  
pp. 489-500 ◽  
Author(s):  
Stuart A. MacNeill
Keyword(s):  
Replication Fork ◽  
Biochemical Analysis ◽  
Current Knowledge ◽  
Chromosomal Dna ◽  
Minichromosome Maintenance ◽  
Replication Process ◽  
Replicative Helicase ◽  
Cellular Life ◽  
Mcm Helicase ◽  
And Function

High-fidelity chromosomal DNA replication is fundamental to all forms of cellular life and requires the complex interplay of a wide variety of essential and non-essential protein factors in a spatially and temporally co-ordinated manner. In eukaryotes, the GINS complex (from the Japanese go-ichi-ni-san meaning 5-1-2-3, after the four related subunits of the complex Sld5, Psf1, Psf2 and Psf3) was recently identified as a novel factor essential for both the initiation and elongation stages of the replication process. Biochemical analysis has placed GINS at the heart of the eukaryotic replication apparatus as a component of the CMG [Cdc45–MCM (minichromosome maintenance) helicase–GINS] complex that most likely serves as the replicative helicase, unwinding duplex DNA ahead of the moving replication fork. GINS homologues are found in the archaea and have been shown to interact directly with the MCM helicase and with primase, suggesting a central role for the complex in archaeal chromosome replication also. The present review summarizes current knowledge of the structure, function and evolution of the GINS complex in eukaryotes and archaea, discusses possible functions of the GINS complex and highlights recent results that point to possible regulation of GINS function in response to DNA damage.

The MCM complex: (just) a replicative helicase?

2008 ◽  
Vol 36 (1) ◽  
pp. 136-140 ◽  
Author(s):  
Alessandro Costa ◽  
Silvia Onesti
Keyword(s):  
Minichromosome Maintenance ◽  
Replicative Helicase ◽  
Aaa Atpase ◽  
Mcm Helicase ◽  
Eukaryotic Dna ◽  
Mcm Complex ◽  
Elongation Step ◽  
Hexameric Helicases

The MCM2–MCM7 (minichromosome maintenance 2–7) complex is involved both in the initiation and the elongation step of eukaryotic DNA replication and is believed to be the replicative helicase. Whereas the mechanism of DNA unwinding at the replication fork has been extensively investigated, the role of the MCM2–MCM7 complex during initiation has not yet been characterized by biochemical studies. Here we summarize the in vivo evidence which supports a role for the MCM complex in origin melting. In addition, we present an overview of the mechanism of action of a number of AAA+ (ATPase associated with various cellular activities) initiators and hexameric helicases, which can be used in turn as models for the steps of recognition, duplex melting, loading and nucleic acid translocation of the MCM helicase.

The MCM helicase: linking checkpoints to the replication fork

2008 ◽  
Vol 36 (1) ◽  
pp. 114-119 ◽  
Author(s):  
Susan L. Forsburg
Keyword(s):  
Dna Replication ◽  
Replication Fork ◽  
Genome Integrity ◽  
Minichromosome Maintenance ◽  
Replication Checkpoint ◽  
Checkpoint Kinases ◽  
Mcm Helicase ◽  
Mcm Proteins

The MCM (minichromosome maintenance) complex is a helicase which is essential for DNA replication. Recent results suggest that the MCM helicase is important for replication fork integrity, and may function as a target of the replication checkpoint. Interactions between MCM proteins, checkpoint kinases, and repair and recovery proteins suggest that MCMs are proximal effectors of replication fork stability in the cell and are likely to play an important role in maintaining genome integrity.

scholarly journals Archaeal MCM Proteins as an Analog for the Eukaryotic Mcm2–7 Helicase to Reveal Essential Features of Structure and Function

Archaea ◽  
2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Justin M. Miller ◽  
Eric J. Enemark
Keyword(s):  
Replication Fork ◽  
Structure And Function ◽  
Replicative Helicase ◽  
The Core ◽  
Mcm Helicase ◽  
Mcm Proteins ◽  
And Function ◽  
Related Proteins

In eukaryotes, the replicative helicase is the large multisubunit CMG complex consisting of the Mcm2–7 hexameric ring, Cdc45, and the tetrameric GINS complex. The Mcm2–7 ring assembles from six different, related proteins and forms the core of this complex. In archaea, a homologous MCM hexameric ring functions as the replicative helicase at the replication fork. Archaeal MCM proteins form thermostable homohexamers, facilitating their use as models of the eukaryotic Mcm2–7 helicase. Here we review archaeal MCM helicase structure and function and how the archaeal findings relate to the eukaryotic Mcm2–7 ring.

scholarly journals The yeast S phase checkpoint enables replicating chromosomes to bi-orient and restrain spindle extension during S phase distress

2005 ◽  
Vol 168 (7) ◽  
pp. 999-1012 ◽  
Author(s):  
Jeff Bachant ◽  
Shannon R. Jessen ◽  
Sarah E. Kavanaugh ◽  
Candida S. Fielding
Keyword(s):  
Dna Replication ◽  
Chromosome Segregation ◽  
Replication Fork ◽  
S Phase ◽  
Origin Of Replication ◽  
Independent Manner ◽  
Checkpoint Signaling ◽  
Hydroxyurea Treatment ◽  
Chromatid Cohesion ◽  
S Phase Checkpoint

The budding yeast S phase checkpoint responds to hydroxyurea-induced nucleotide depletion by preventing replication fork collapse and the segregation of unreplicated chromosomes. Although the block to chromosome segregation has been thought to occur by inhibiting anaphase, we show checkpoint-defective rad53 mutants undergo cycles of spindle extension and collapse after hydroxyurea treatment that are distinct from anaphase cells. Furthermore, chromatid cohesion, whose dissolution triggers anaphase, is dispensable for S phase checkpoint arrest. Kinetochore–spindle attachments are required to prevent spindle extension during replication blocks, and chromosomes with two centromeres or an origin of replication juxtaposed to a centromere rescue the rad53 checkpoint defect. These observations suggest that checkpoint signaling is required to generate an inward force involved in maintaining preanaphase spindle integrity during DNA replication distress. We propose that by promoting replication fork integrity under these conditions Rad53 ensures centromere duplication. Replicating chromosomes can then bi-orient in a cohesin-independent manner to restrain untimely spindle extension.

scholarly journals DNA Binding by the Methanothermobacter thermautotrophicus Cdc6 Protein Is Inhibited by the Minichromosome Maintenance Helicase

2006 ◽  
Vol 188 (12) ◽  
pp. 4577-4580 ◽  
Author(s):  
Rajesh Kasiviswanathan ◽  
Jae-Ho Shin ◽  
Zvi Kelman
Keyword(s):  
Dna Binding ◽  
Binding Activity ◽  
Minichromosome Maintenance ◽  
Single Stranded Dna ◽  
Mutant Proteins ◽  
Dna Binding Activity ◽  
Double Stranded Dna ◽  
Mcm Helicase ◽  
Methanothermobacter Thermautotrophicus

ABSTRACT The Cdc6 proteins from the archaeon Methanothermobacter thermautotrophicus were previously shown to bind double-stranded DNA. It is shown here that the proteins also bind single-stranded DNA. Using minichromosome maintenance (MCM) helicase mutant proteins unable to bind DNA, it was found that the interaction of MCM with Cdc6 inhibits the DNA binding activity of Cdc6.

scholarly journals Replication fork stalling elicits chromatin compaction for the stability of stalling replication forks

2019 ◽  
Vol 116 (29) ◽  
pp. 14563-14572 ◽  
Author(s):  
Gang Feng ◽  
Yue Yuan ◽  
Zeyang Li ◽  
Lu Wang ◽  
Bo Zhang ◽  
...  
Keyword(s):  
Replication Fork ◽  
Cellular Mechanism ◽  
Eukaryotic Cells ◽  
Replication Forks ◽  
Physical Separation ◽  
Replicative Helicase ◽  
Chromatin Compaction ◽  
Acetylation Site ◽  
Fork Stalling ◽  
The Stability

DNA replication forks in eukaryotic cells stall at a variety of replication barriers. Stalling forks require strict cellular regulations to prevent fork collapse. However, the mechanism underlying these cellular regulations is poorly understood. In this study, a cellular mechanism was uncovered that regulates chromatin structures to stabilize stalling forks. When replication forks stall, H2BK33, a newly identified acetylation site, is deacetylated and H3K9 trimethylated in the nucleosomes surrounding stalling forks, which results in chromatin compaction around forks. Acetylation-mimic H2BK33Q and its deacetylase clr6-1 mutations compromise this fork stalling-induced chromatin compaction, cause physical separation of replicative helicase and DNA polymerases, and significantly increase the frequency of stalling fork collapse. Furthermore, this fork stalling-induced H2BK33 deacetylation is independent of checkpoint. In summary, these results suggest that eukaryotic cells have developed a cellular mechanism that stabilizes stalling forks by targeting nucleosomes and inducing chromatin compaction around stalling forks. This mechanism is named the “Chromsfork” control: Chromatin Compaction Stabilizes Stalling Replication Forks.

scholarly journals Polymorphism and Double Hexamer Structure in the Archaeal Minichromosome Maintenance (MCM) Helicase fromMethanobacterium thermoautotrophicum

2005 ◽  
Vol 280 (49) ◽  
pp. 40909-40915 ◽  
Author(s):  
Yacob Gómez-Llorente ◽  
Ryan J. Fletcher ◽  
Xiaojiang S. Chen ◽  
José M. Carazo ◽  
Carmen San Martín
Keyword(s):  
Minichromosome Maintenance ◽  
Mcm Helicase

scholarly journals The interplay of DNA binding, ATP hydrolysis and helicase activities of the archaeal MCM helicase

2011 ◽  
Vol 436 (2) ◽  
pp. 409-414 ◽  
Author(s):  
Li Phing Liew ◽  
Stephen D. Bell
Keyword(s):  
Dna Binding ◽  
Active Site ◽  
Atp Hydrolysis ◽  
Sulfolobus Solfataricus ◽  
Active Form ◽  
Dna Helicase ◽  
Atpase Domain ◽  
Minichromosome Maintenance ◽  
Conserved Residues ◽  
Mcm Helicase

The MCM (minichromosome maintenance) proteins of archaea are widely believed to be the replicative DNA helicase of these organisms. Most archaea possess a single MCM orthologue that forms homo-multimeric assemblies with a single hexamer believed to be the active form. In the present study we characterize the roles of highly conserved residues in the ATPase domain of the MCM of the hyperthermophilic archaeon Sulfolobus solfataricus. Our results identify a potential conduit for communicating DNA-binding information to the ATPase active site.

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