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DNA Repair Dec 2021Unlike all other biological molecules that are degraded and replaced if damaged, DNA must be repaired as chromosomes cannot be replaced. Indeed, DNA endures a wide... (Review)
Review
Unlike all other biological molecules that are degraded and replaced if damaged, DNA must be repaired as chromosomes cannot be replaced. Indeed, DNA endures a wide variety of structural damage that need to be repaired accurately to maintain genomic stability and proper functioning of cells and to prevent mutation leading to disease. Given that the genome is packaged into chromatin within eukaryotic cells, it has become increasingly evident that the chromatin context of DNA both facilitates and regulates DNA repair processes. In this review, we discuss mechanisms involved in removal of histones (chromatin disassembly) from around DNA lesions, by histone chaperones and chromatin remodelers, that promotes accessibility of the DNA repair machinery. We also elaborate on how the deposition of core histones and specific histone variants onto DNA (chromatin assembly) during DNA repair promotes repair processes, the role of histone post translational modifications in these processes and how chromatin structure is reestablished after DNA repair is complete.
Topics: Animals; Chromatin; Chromatin Assembly and Disassembly; DNA Repair; Histones; Humans
PubMed: 34687987
DOI: 10.1016/j.dnarep.2021.103240 -
Current Opinion in Structural Biology Jun 2023Heterochromatin formation has been proposed to involve phase transitions on the level of the three-dimensional folding of heterochromatin regions and the liquid-liquid... (Review)
Review
Heterochromatin formation has been proposed to involve phase transitions on the level of the three-dimensional folding of heterochromatin regions and the liquid-liquid demixing of heterochromatin proteins. Here, I outline the hallmarks of such transitions and the current challenges to detect them in living cells. I further discuss the abundance and properties of prominent heterochromatin proteins and relate them to their potential role in driving phase transitions. Recent data from mouse fibroblasts indicate that pericentric heterochromatin is organized via a reordering transition on the level of heterochromatin regions that does not necessarily involve liquid-liquid demixing of heterochromatin proteins. Evaluating key hallmarks of the different candidate phase transition mechanisms across cell types and species will be needed to complete the current picture.
Topics: Animals; Mice; Heterochromatin; Chromatin Assembly and Disassembly
PubMed: 37087823
DOI: 10.1016/j.sbi.2023.102597 -
Annals of Biomedical Engineering Oct 2009Nanobiotechnology involves the creation, characterization, and modification of organized nanomaterials to serve as building blocks for constructing nanoscale devices in... (Review)
Review
Nanobiotechnology involves the creation, characterization, and modification of organized nanomaterials to serve as building blocks for constructing nanoscale devices in technology and medicine. Living systems contain a wide variety of nanomachines and highly ordered structures of macromolecules. The novelty and ingenious design of the bacterial virus phi29 DNA packaging motor and its parts inspired the synthesis of this motor and its components as biomimetics. This 30-nm nanomotor uses six copies of an ATP-binding pRNA to gear the motor. The structural versatility of pRNA has been utilized to construct dimers, trimers, hexamers, and patterned superstructures via the interaction of two interlocking loops. The approach, based on bottom-up assembly, has also been applied to nanomachine fabrication, pathogen detection and the delivery of drugs, siRNA, ribozymes, and genes to specific cells in vitro and in vivo. Another essential component of the motor is the connector, which contains 12 copies of a protein gp10 to form a 3.6-nm central channel as a path for DNA. This article will review current studies of the structure and function of the phi29 DNA packaging motor, as well as the mechanism of motion, the principle of in vitro construction, and its potential nanotechnological and medical applications.
Topics: Adenosine Triphosphate; Bacillus Phages; Capsid; DNA; DNA Packaging; Genetic Therapy; Molecular Motor Proteins; Nanomedicine; RNA
PubMed: 19495981
DOI: 10.1007/s10439-009-9723-0 -
DNA Repair Aug 2022Most eukaryotic DNA is packaged into chromatin, which is made up of tandemly repeating nucleosomes. This packaging of DNA poses a significant barrier to the various... (Review)
Review
Most eukaryotic DNA is packaged into chromatin, which is made up of tandemly repeating nucleosomes. This packaging of DNA poses a significant barrier to the various enzymes that must act on DNA, including DNA damage response enzymes that interact intimately with DNA to prevent mutations and cell death. To regulate access to certain DNA regions, chromatin remodeling, variant histone exchange, and histone post-translational modifications have been shown to assist several DNA repair pathways including nucleotide excision repair, single strand break repair, and double strand break repair. While these chromatin-level responses have been directly linked to various DNA repair pathways, how they modulate the base excision repair (BER) pathway remains elusive. This review highlights recent findings that demonstrate how BER is regulated by the packaging of DNA into nucleosome core particles (NCPs) and higher orders of chromatin structures. We also summarize the available data that indicate BER may be enabled by chromatin modifications and remodeling.
Topics: Chromatin; Chromatin Assembly and Disassembly; DNA; DNA Damage; DNA Repair; Histones; Nucleosomes
PubMed: 35689883
DOI: 10.1016/j.dnarep.2022.103345 -
Annual Review of Virology Nov 2015Translocation of viral double-stranded DNA (dsDNA) into the icosahedral prohead shell is catalyzed by TerL, a motor protein that has ATPase, endonuclease, and... (Review)
Review
Translocation of viral double-stranded DNA (dsDNA) into the icosahedral prohead shell is catalyzed by TerL, a motor protein that has ATPase, endonuclease, and translocase activities. TerL, following endonucleolytic cleavage of immature viral DNA concatemer recognized by TerS, assembles into a pentameric ring motor on the prohead's portal vertex and uses ATP hydrolysis energy for DNA translocation. TerL's N-terminal ATPase is connected by a hinge to the C-terminal endonuclease. Inchworm models propose that modest domain motions accompanying ATP hydrolysis are amplified, through changes in electrostatic interactions, into larger movements of the C-terminal domain bound to DNA. In phage ϕ29, four of the five TerL subunits sequentially hydrolyze ATP, each powering translocation of 2.5 bp. After one viral genome is encapsidated, the internal pressure signals termination of packaging and ejection of the motor. Current focus is on the structures of packaging complexes and the dynamics of TerL during DNA packaging, endonuclease regulation, and motor mechanics.
Topics: DNA Packaging; DNA Viruses; DNA, Viral; Viral Proteins; Virus Assembly
PubMed: 26958920
DOI: 10.1146/annurev-virology-100114-055212 -
Blood Jun 2022
Topics: Chromatin Assembly and Disassembly; DNA Repair; Epigenesis, Genetic; Epigenome
PubMed: 35679076
DOI: 10.1182/blood.2022016176 -
Cell Cycle (Georgetown, Tex.) 2018The timely and precise repair of DNA damage, or more specifically DNA double-strand breaks (DSBs) - the most deleterious DNA lesions, is crucial for maintaining genome... (Review)
Review
The timely and precise repair of DNA damage, or more specifically DNA double-strand breaks (DSBs) - the most deleterious DNA lesions, is crucial for maintaining genome integrity and cellular homeostasis. An appropriate cellular response to DNA DSBs requires the integration of various factors, including the post-translational modifications (PTMs) of chromatin and chromatin-associated proteins. Notably, the PTMs of histones have been shown to play a fundamental role in initiating and regulating cellular responses to DNA DSBs. Here we review the role of the major histone PTMs, including phosphorylation, ubiquitination, methylation and acetylation, and their interactions during DNA DSB-induced responses.
Topics: Animals; Chromatin Assembly and Disassembly; DNA Breaks, Double-Stranded; DNA Repair; Histones; Humans; Protein Processing, Post-Translational
PubMed: 30394812
DOI: 10.1080/15384101.2018.1542899 -
Chromosoma Apr 2012Inefficient and inaccurate repair of DNA damage is the principal cause of DNA mutations, chromosomal aberrations, and carcinogenesis. Numerous multiple-step DNA repair... (Review)
Review
Inefficient and inaccurate repair of DNA damage is the principal cause of DNA mutations, chromosomal aberrations, and carcinogenesis. Numerous multiple-step DNA repair pathways exist whose deployment depends on the nature of the DNA lesion. Common to all eukaryotic DNA repair pathways is the need to unravel the compacted chromatin structure to facilitate access of the repair machinery to the DNA and restoration of the original chromatin state afterward. Accordingly, our cells utilize a plethora of coordinated mechanisms to locally open up the chromatin structure to reveal the underlying DNA sequence and to orchestrate the efficient and accurate repair of DNA lesions. Here we review changes to the chromatin structure that are intrinsic to the DNA damage response and the available mechanistic insight into how these chromatin changes facilitate distinct stages of the DNA damage repair pathways to maintain genomic stability.
Topics: Chromatin Assembly and Disassembly; DNA Breaks, Double-Stranded; DNA Repair; Epigenesis, Genetic; Genomic Instability; Histones; Models, Biological
PubMed: 22249206
DOI: 10.1007/s00412-011-0358-1 -
Genome Dynamics 2007We present an overview of comparative genomics of ATP-dependent DNA packaging systems of viruses. Several distinct ATPase motors and accessory proteins have been... (Comparative Study)
Comparative Study Review
We present an overview of comparative genomics of ATP-dependent DNA packaging systems of viruses. Several distinct ATPase motors and accessory proteins have been identified in DNA-packaging systems of viruses such as terminase-portal systems, the 29-like packaging apparatus, and packaging systems of lipid inner-membrane-containing viruses. Sequence and structure analysis of these proteins suggest that there were two major independent innovations of ATP-dependent DNA packaging systems in the viral universe. The first of these utilizes a HerA/FtsK superfamily ATPase and is seen in prokaryotic viruses with inner lipid membranes, large eukaryotic nucleo-cytoplasmic DNA viruses (including poxviruses) and a group of eukaryotic mobile DNA transposons. We show that ATPases of the 29-like packaging system are also divergent versions of the HerA/FtsK superfamily that functions in viruses without an inner membrane. The second system, the terminase-portal system, is dominant in prokaryotic tailed viruses and typically functions with linear chromosomes. The large subunit of this system contains a distinct ATPase domain and a C-terminal nuclease domain of the RNAse H fold. We discuss the classification of these ATPases within the P-loop NTPases, genomic demography and positioning of their genes in the viral chromosome. We show that diverse portal proteins utilized by these systems share a common evolutionary origin and might have frequently displaced each other in evolution. Examination of conserved gene neighborhoods indicates repeated acquisition of Helix-turn-Helix domain-containing terminase small subunits and a third accessory component, the MuF protein. Adenoviruses appear to have evolved a third packaging ATPase, unique to their lineage. Relationship between one major type of packaging ATPases and cellular chromosome pumps like FtsK suggests an ancient common origin for viral packaging and cellular chromosome partitioning systems.
Topics: Adenosine Triphosphatases; Adenosine Triphosphate; DNA Packaging; DNA, Viral; Evolution, Molecular; Genomics
PubMed: 18753784
DOI: 10.1159/000107603 -
Current Opinion in Virology Jun 2019During the assembly of dsDNA viruses such as the tailed bacteriophages and herpesviruses, the viral chromosome is compacted to near crystalline density inside a... (Review)
Review
During the assembly of dsDNA viruses such as the tailed bacteriophages and herpesviruses, the viral chromosome is compacted to near crystalline density inside a preformed head shell. DNA translocation is driven by powerful ring ATPase motors that couple ATP binding, hydrolysis, and release to force generation and movement. Studies of the motor of the bacteriophage phi29 have revealed a complex mechanochemistry behind this process that slows as the head fills. Recent studies of the physical behavior of packaging DNA suggest that surprisingly long-time scales of relaxation of DNA inside the head and jamming phenomena during packaging create the physical need for regulation of the rate of packaging. Studies of DNA packaging in viral systems have, therefore, revealed fundamental insight into the complex behavior of DNA and the need for biological systems to accommodate these physical constraints.
Topics: Adenosine Triphosphate; Bacteriophages; DNA Packaging; DNA, Viral; Models, Molecular; Translocation, Genetic; Viral Proteins; Virus Assembly; Viruses
PubMed: 31003199
DOI: 10.1016/j.coviro.2019.03.002