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

Miller, Justin M.; Enemark, Eric J.

doi:10.1155/2015/305497

Cited by 21 publications

(25 citation statements)

References 89 publications

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“…This model requires cooperativity between N‐ and C‐tiers, both of which bind DNA. DNA binding to both the N‐tier and C‐tier of S.c. CMG and an archaeal MCM has been demonstrated . Interestingly, DNA is bound to the C‐tier of D.m.…”

Section: The Mechanism Of Cmg Translocation Along Dnamentioning

confidence: 99%

The Eukaryotic CMG Helicase at the Replication Fork: Emerging Architecture Reveals an Unexpected Mechanism

O'Donnell

2018

BioEssays

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The eukaryotic helicase is an 11-subunit machine containing an Mcm2-7 motor ring that encircles DNA, Cdc45 and the GINS tetramer, referred to as CMG (Cdc45, Mcm2-7, GINS). CMG is "built" on DNA at origins in two steps. First, two Mcm2-7 rings are assembled around duplex DNA at origins in G1 phase, forming the Mcm2-7 "double hexamer." In a second step, in S phase Cdc45 and GINS are assembled onto each Mcm2-7 ring, hence producing two CMGs that ultimately form two replication forks that travel in opposite directions. Here, we review recent findings about CMG structure and function. The CMG unwinds the parental duplex and is also the organizing center of the replisome: it binds DNA polymerases and other factors. EM studies reveal a 20-subunit core replisome with the leading Pol ϵ and lagging Pol α-primase on opposite faces of CMG, forming a fundamentally asymmetric architecture. Structural studies of CMG at a replication fork reveal unexpected details of how CMG engages the DNA fork. The structures of CMG and the Mcm2-7 double hexamer on DNA suggest a completely unanticipated process for formation of bidirectional replication forks at origins.

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Section: The Mechanism Of Cmg Translocation Along Dnamentioning

confidence: 99%

The Eukaryotic CMG Helicase at the Replication Fork: Emerging Architecture Reveals an Unexpected Mechanism

O'Donnell

2018

BioEssays

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“…(1) α Helices in the regulatory subdomain A form a compact bundle on the outside of the helicase ring. This domain has been suggested to regulate MCM helicase activity and function as a conformational switch in archaea (Slaymaker and Chen 2012;Miller and Enemark 2015). Its role in eukaryotes is less clear.…”

Section: General Organization Of MCMmentioning

confidence: 99%

From structure to mechanism—understanding initiation of DNA replication

et al. 2017

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DNA replication results in the doubling of the genome prior to cell division. This process requires the assembly of 50 or more protein factors into a replication fork. Here, we review recent structural and biochemical insights that start to explain how specific proteins recognize DNA replication origins, load the replicative helicase on DNA, unwind DNA, synthesize new DNA strands, and reassemble chromatin. We focus on the minichromosome maintenance (MCM2-7) proteins, which form the core of the eukaryotic replication fork, as this complex undergoes major structural rearrangements in order to engage with DNA, regulate its DNA-unwinding activity, and maintain genome stability.

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“…Based on this similarity, these protein complexes are termed “molecular machines” [ 2 ]. A diverse set of molecular machines are required for a myriad of cellular functions including DNA replication [ 3 , 4 ] and recombination [ 5 ], regulated proteolysis [ 6 – 8 ], protein disaggregation [ 9 – 12 ], protein complex disassembly [ 13 ], and many others.…”

Section: Molecular Machines Are Ubiquitous In the Cellmentioning

confidence: 99%

“…Many AAA+ proteins share a common protein/DNA remodeling or degradation function where the energy of ATP hydrolysis is coupled to translocation along polymeric substrates [ 3 , 6 , 7 , 14 , 40 , 41 , 75 – 82 ]. These proteins commonly form a closed ring that positions central channel loops to interact with encircled DNA or polypeptide.…”

Section: Archaeal Aaa+ Hexamers Share Common Structural and Functimentioning

confidence: 99%

Fundamental Characteristics of AAA+ Protein Family Structure and Function

Miller

Enemark

2016

Archaea

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Many complex cellular events depend on multiprotein complexes known as molecular machines to efficiently couple the energy derived from adenosine triphosphate hydrolysis to the generation of mechanical force. Members of the AAA+ ATPase superfamily (ATPases Associated with various cellular Activities) are critical components of many molecular machines. AAA+ proteins are defined by conserved modules that precisely position the active site elements of two adjacent subunits to catalyze ATP hydrolysis. In many cases, AAA+ proteins form a ring structure that translocates a polymeric substrate through the central channel using specialized loops that project into the central channel. We discuss the major features of AAA+ protein structure and function with an emphasis on pivotal aspects elucidated with archaeal proteins.

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

Cited by 21 publications

References 89 publications

The Eukaryotic CMG Helicase at the Replication Fork: Emerging Architecture Reveals an Unexpected Mechanism

The Eukaryotic CMG Helicase at the Replication Fork: Emerging Architecture Reveals an Unexpected Mechanism

From structure to mechanism—understanding initiation of DNA replication

Fundamental Characteristics of AAA+ Protein Family Structure and Function

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