Molecular Mechanisms of the Functional Coupling of the Helicase (gp41) and Polymerase (gp43) of Bacteriophage T4 within the DNA Replication Fork†

Biochemistry ◽  
2001 ◽  
Vol 40 (14) ◽  
pp. 4459-4477 ◽  
Author(s):  
Emmanuelle Delagoutte ◽  
Peter H. von Hippel
Keyword(s):  
Dna Replication ◽  
Replication Fork ◽  
Molecular Mechanisms ◽  
Bacteriophage T4 ◽  
Functional Coupling

scholarly journals Dual Functions of Single-stranded DNA-binding Protein in Helicase Loading at the Bacteriophage T4 DNA Replication Fork

2004 ◽  
Vol 279 (18) ◽  
pp. 19035-19045 ◽  
Author(s):  
Yujie Ma ◽  
Tongsheng Wang ◽  
Jana L. Villemain ◽  
David P. Giedroc ◽  
Scott W. Morrical
Keyword(s):  
Dna Replication ◽  
Dna Binding ◽  
Replication Fork ◽  
Binding Protein ◽  
Bacteriophage T4 ◽  
Dna Binding Protein ◽  
Single Stranded Dna ◽  
Helicase Loading ◽  
Dual Functions

scholarly journals Protein-Protein and Protein-DNA Interactions at the Bacteriophage T4 DNA Replication Fork

1996 ◽  
Vol 271 (45) ◽  
pp. 28045-28051 ◽  
Author(s):  
Daniel J. Sexton ◽  
Theodore E. Carver ◽  
Anthony J. Berdis ◽  
Stephen J. Benkovic
Keyword(s):  
Dna Replication ◽  
Replication Fork ◽  
Bacteriophage T4 ◽  
Dna Interactions ◽  
Protein Dna Interactions

scholarly journals Using Site Specific Fluorescent Probes to Examine Replication Fork Destabilization by Regulatory Proteins of the Bacteriophage T4 DNA Replication Complex

2017 ◽  
Vol 112 (3) ◽  
pp. 314a-315a
Author(s):  
Davis Jose ◽  
Miya Mary Michael ◽  
Wonbae Lee ◽  
Thomas H. Steinberg ◽  
Andrew H. Marcus ◽  
...  
Keyword(s):  
Dna Replication ◽  
Fluorescent Probes ◽  
Replication Fork ◽  
Bacteriophage T4 ◽  
Regulatory Proteins ◽  
Site Specific ◽  
Replication Complex

scholarly journals Replication fork dynamics and the DNA damage response

2012 ◽  
Vol 443 (1) ◽  
pp. 13-26 ◽  
Author(s):  
Rebecca M. Jones ◽  
Eva Petermann
Keyword(s):  
Dna Damage ◽  
Dna Replication ◽  
Dna Damage Response ◽  
Replication Fork ◽  
Molecular Mechanisms ◽  
S Phase ◽  
Replication Initiation ◽  
Developmental Defects ◽  
Replication Fork Progression ◽  
Damage Response

Prevention and repair of DNA damage is essential for maintenance of genomic stability and cell survival. DNA replication during S-phase can be a source of DNA damage if endogenous or exogenous stresses impair the progression of replication forks. It has become increasingly clear that DNA-damage-response pathways do not only respond to the presence of damaged DNA, but also modulate DNA replication dynamics to prevent DNA damage formation during S-phase. Such observations may help explain the developmental defects or cancer predisposition caused by mutations in DNA-damage-response genes. The present review focuses on molecular mechanisms by which DNA-damage-response pathways control and promote replication dynamics in vertebrate cells. In particular, DNA damage pathways contribute to proper replication by regulating replication initiation, stabilizing transiently stalled forks, promoting replication restart and facilitating fork movement on difficult-to-replicate templates. If replication fork progression fails to be rescued, this may lead to DNA damage and genomic instability via nuclease processing of aberrant fork structures or incomplete sister chromatid separation during mitosis.

scholarly journals RecG and UvsW catalyse robust DNA rewinding critical for stalled DNA replication fork rescue

2013 ◽  
Vol 4 (1) ◽  
Author(s):  
Maria Manosas ◽  
Senthil K. Perumal ◽  
Piero R. Bianco ◽  
Felix Ritort ◽  
Stephen J. Benkovic ◽  
...  
Keyword(s):  
Dna Repair ◽  
Dna Replication ◽  
Single Molecule ◽  
Replication Fork ◽  
Genetic Recombination ◽  
Bacteriophage T4 ◽  
General Mechanism ◽  
Dna Unwinding ◽  
Replication Forks ◽  
Displacement Reactions

Abstract Helicases that both unwind and rewind DNA have central roles in DNA repair and genetic recombination. In contrast to unwinding, DNA rewinding by helicases has proved difficult to characterize biochemically because of its thermodynamically downhill nature. Here we use single-molecule assays to mechanically destabilize a DNA molecule and follow, in real time, unwinding and rewinding by two DNA repair helicases, bacteriophage T4 UvsW and Escherichia coli RecG. We find that both enzymes are robust rewinding enzymes, which can work against opposing forces as large as 35 pN, revealing their active character. The generation of work during the rewinding reaction allows them to couple rewinding to DNA unwinding and/or protein displacement reactions central to the rescue of stalled DNA replication forks. The overall results support a general mechanism for monomeric rewinding enzymes.

scholarly journals Functional Coupling between DNA Replication and Sister Chromatid Cohesion Establishment

2021 ◽  
Vol 22 (6) ◽  
pp. 2810
Author(s):  
Ana Boavida ◽  
Diana Santos ◽  
Mohammad Mahtab ◽  
Francesca M. Pisani
Keyword(s):  
Dna Replication ◽  
Sister Chromatid ◽  
Molecular Mechanisms ◽  
Sister Chromatid Cohesion ◽  
Functional Coupling ◽  
Functional Link ◽  
Chromatid Cohesion ◽  
Evolutionarily Conserved ◽  
Eukaryotic Organisms ◽  
Replication Factors

Several lines of evidence suggest the existence in the eukaryotic cells of a tight, yet largely unexplored, connection between DNA replication and sister chromatid cohesion. Tethering of newly duplicated chromatids is mediated by cohesin, an evolutionarily conserved hetero-tetrameric protein complex that has a ring-like structure and is believed to encircle DNA. Cohesin is loaded onto chromatin in telophase/G1 and converted into a cohesive state during the subsequent S phase, a process known as cohesion establishment. Many studies have revealed that down-regulation of a number of DNA replication factors gives rise to chromosomal cohesion defects, suggesting that they play critical roles in cohesion establishment. Conversely, loss of cohesin subunits (and/or regulators) has been found to alter DNA replication fork dynamics. A critical step of the cohesion establishment process consists in cohesin acetylation, a modification accomplished by dedicated acetyltransferases that operate at the replication forks. Defects in cohesion establishment give rise to chromosome mis-segregation and aneuploidy, phenotypes frequently observed in pre-cancerous and cancerous cells. Herein, we will review our present knowledge of the molecular mechanisms underlying the functional link between DNA replication and cohesion establishment, a phenomenon that is unique to the eukaryotic organisms.

scholarly journals DNA Helicase–Polymerase Coupling in Bacteriophage DNA Replication

Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1739
Author(s):  
Chen-Yu Lo ◽  
Yang Gao
Keyword(s):  
Dna Replication ◽  
Dna Polymerase ◽  
Molecular Mechanisms ◽  
Bacteriophage T4 ◽  
Dna Helicase ◽  
Model Systems ◽  
Genome Replication ◽  
Template Strand ◽  
Replication Systems ◽  
Mechanistic Basis

Bacteriophages have long been model systems to study the molecular mechanisms of DNA replication. During DNA replication, a DNA helicase and a DNA polymerase cooperatively unwind the parental DNA. By surveying recent data from three bacteriophage replication systems, we summarized the mechanistic basis of DNA replication by helicases and polymerases. Kinetic data have suggested that a polymerase or a helicase alone is a passive motor that is sensitive to the base-pairing energy of the DNA. When coupled together, the helicase–polymerase complex is able to unwind DNA actively. In bacteriophage T7, helicase and polymerase reside right at the replication fork where the parental DNA is separated into two daughter strands. The two motors pull the two daughter strands to opposite directions, while the polymerase provides a separation pin to split the fork. Although independently evolved and containing different replisome components, bacteriophage T4 replisome shares mechanistic features of Hel–Pol coupling that are similar to T7. Interestingly, in bacteriophages with a limited size of genome like Φ29, DNA polymerase itself can form a tunnel-like structure, which encircles the DNA template strand and facilitates strand displacement synthesis in the absence of a helicase. Studies on bacteriophage replication provide implications for the more complicated replication systems in bacteria, archaeal, and eukaryotic systems, as well as the RNA genome replication in RNA viruses.

scholarly journals Molecular mechanisms of eukaryotic origin initiation, replication fork progression, and chromatin maintenance

2020 ◽  
Vol 477 (18) ◽  
pp. 3499-3525
Author(s):  
Zuanning Yuan ◽  
Huilin Li
Keyword(s):  
Dna Replication ◽  
Dna Polymerase ◽  
Replication Fork ◽  
Dna Methyltransferase ◽  
Molecular Mechanisms ◽  
Methylation Pattern ◽  
Replication Initiation ◽  
Nucleosome Assembly ◽  
Epigenetic Information ◽  
Eukaryotic Origin

Eukaryotic DNA replication is a highly dynamic and tightly regulated process. Replication involves several dozens of replication proteins, including the initiators ORC and Cdc6, replicative CMG helicase, DNA polymerase α-primase, leading-strand DNA polymerase ε, and lagging-strand DNA polymerase δ. These proteins work together in a spatially and temporally controlled manner to synthesize new DNA from the parental DNA templates. During DNA replication, epigenetic information imprinted on DNA and histone proteins is also copied to the daughter DNA to maintain the chromatin status. DNA methyltransferase 1 is primarily responsible for copying the parental DNA methylation pattern into the nascent DNA. Epigenetic information encoded in histones is transferred via a more complex and less well-understood process termed replication-couple nucleosome assembly. Here, we summarize the most recent structural and biochemical insights into DNA replication initiation, replication fork elongation, chromatin assembly and maintenance, and related regulatory mechanisms.

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