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.

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.

The haloarchaeal chromosome replication machinery

2009 ◽  
Vol 37 (1) ◽  
pp. 108-113 ◽  
Author(s):  
Stuart A. MacNeill
Keyword(s):  
Dna Replication ◽  
Replication Fork ◽  
Biochemical Analysis ◽  
Structure And Function ◽  
Haloferax Volcanii ◽  
Eukaryotic Cells ◽  
Replication Machinery ◽  
Chromosomal Dna ◽  
Biochemical Studies ◽  
And Function

The powerful combination of genetic and biochemical analysis has provided many key insights into the structure and function of the chromosomal DNA replication machineries of bacterial and eukaryotic cells. In contrast, in the archaea, biochemical studies have dominated, mainly due to the absence of efficient genetic systems for these organisms. This situation is changing, however, and, in this regard, the genetically tractable haloarchaea Haloferax volcanii and Halobacterium sp. NRC-1 are emerging as key models. In the present review, I give an overview of the components of the replication machinery in the haloarchaea, with particular emphasis on the protein factors presumed to travel with the replication fork.

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 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.

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.

scholarly journals Two essential replicative DNA polymerases exchange dynamically during DNA replication and after replication fork arrest

2018 ◽  
Author(s):  
Yilai Li ◽  
Ziyuan Chen ◽  
Lindsay A. Matthews ◽  
Lyle A. Simmons ◽  
Julie S. Biteen
Keyword(s):  
Dna Replication ◽  
Single Molecule ◽  
Replication Fork ◽  
Dna Polymerases ◽  
Super Resolution ◽  
Clamp Loader ◽  
Chromosomal Dna ◽  
Chromosomal Replication ◽  
Replication Process ◽  
Cooperative Process

AbstractThe replisome is the multi-protein complex responsible for faithful replication of chromosomal DNA. Using single-molecule super-resolution imaging, we characterized the dynamics of three replisomal proteins in liveBacillus subtiliscells: the two replicative DNA polymerases, PolC and DnaE, and a processivity clamp loader subunit, DnaX. We quantified the protein mobility and dwell times during normal replication and following both damage-independent and damage-dependent replication fork stress. With these results, we report the dynamic and cooperative process of DNA replication based on changes in the measured diffusion coefficients and dwell times. These experiments show that the replisomal proteins are all highly dynamic and that the exchange rate depends on whether DNA synthesis is active or arrested. Our results also suggest coupling between PolC and DnaX in the DNA replication process, and indicate that DnaX provides an important role in synthesis during repair. Furthermore, our results show that DnaE provides a limited contribution to chromosomal replication and repair.

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 Different Residues on the Surface of theMethanothermobacter thermautotrophicusMCM Helicase Interact with Single- and Double-Stranded DNA

Archaea ◽  
2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Nozomi Sakakibara ◽  
Rajesh Kasiviswanathan ◽  
Zvi Kelman
Keyword(s):  
Opposite Effect ◽  
Chromosomal Dna ◽  
Minichromosome Maintenance ◽  
Conserved Residues ◽  
Replicative Helicase ◽  
Double Stranded Dna ◽  
Archaeal Species ◽  
Mcm Complex ◽  
Protein Multimerization ◽  
Conserved Amino Acids

The minichromosome maintenance (MCM) complex is thought to function as the replicative helicase in archaea, separating the two strands of chromosomal DNA during replication. The catalytic activity resides within the C-terminal region of the MCM protein, while the N-terminal portion plays an important role in DNA binding and protein multimerization. An alignment of MCM homologues from several archaeal species revealed a number of conserved amino acids. Here several of the conserved residues located on the surface of the helicase have been mutated and their roles in MCM functions determined. It was found that some mutations result in increased affinity for ssDNA while the affinity for dsDNA is decreased. Other mutants exhibit the opposite effect. Thus, the data suggest that these conserved surface residues may participate in MCM-DNA interactions.

Effects of Maternal Obesity and Gestational Diabetes Mellitus on the Placenta: Current Knowledge and Targets for Therapeutic Interventions

2020 ◽  
Vol 19 (2) ◽  
pp. 176-192
Author(s):  
Samantha Bedell ◽  
Janine Hutson ◽  
Barbra de Vrijer ◽  
Genevieve Eastabrook
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Maternal Obesity ◽  
Environmental Changes ◽  
Current Knowledge ◽  
Therapeutic Interventions ◽  
Placental Development ◽  
Exchange Site ◽  
And Function

: Obesity and gestational diabetes mellitus (GDM) are becoming more common among pregnant women worldwide and are individually associated with a number of placenta-mediated obstetric complications, including preeclampsia, macrosomia, intrauterine growth restriction and stillbirth. The placenta serves several functions throughout pregnancy and is the main exchange site for the transfer of nutrients and gas from mother to fetus. In pregnancies complicated by maternal obesity or GDM, the placenta is exposed to environmental changes, such as increased inflammation and oxidative stress, dyslipidemia, and altered hormone levels. These changes can affect placental development and function and lead to abnormal fetal growth and development as well as metabolic and cardiovascular abnormalities in the offspring. This review aims to summarize current knowledge on the effects of obesity and GDM on placental development and function. Understanding these processes is key in developing therapeutic interventions with the goal of mitigating these effects and preventing future cardiovascular and metabolic pathology in subsequent generations.

The Oxford Handbook of the Auditory Brainstem

2018 ◽  
Keyword(s):  
Current Knowledge ◽  
Auditory Pathway ◽  
Auditory Brainstem ◽  
Auditory Midbrain ◽  
Current State ◽  
Neuronal Mechanisms ◽  
Maladaptive Plasticity ◽  
And Function ◽  
Auditory Field

The Oxford Handbook of the Auditory Brainstem provides an in-depth reference to the organization and function of ascending and descending auditory pathways in the mammalian brainstem. Individual chapters are organized along the auditory pathway, beginning with the cochlea and ending with the auditory midbrain. Each chapter provides an introduction to the respective area and summarizes our current knowledge before discussing the disputes and challenges that the field currently faces.The handbook emphasizes the numerous forms of plasticity that are increasingly observed in many areas of the auditory brainstem. Several chapters focus on neuronal modulation of function and plasticity on the synaptic, neuronal, and circuit level, especially during development, aging, and following peripheral hearing loss. In addition, the book addresses the role of trauma-induced maladaptive plasticity with respect to its contribution in generating central hearing dysfunction, such as hyperacusis and tinnitus.The book is intended for students and postdoctoral fellows starting in the auditory field and for researchers of related fields who wish to get an authoritative and up-to-date summary of the current state of auditory brainstem research. For clinical practitioners in audiology, otolaryngology, and neurology, the book is a valuable resource of information about the neuronal mechanisms that are currently discussed as major candidates for the generation of central hearing dysfunction.

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