Gene Therapy for Paediatric Homozygous Familial Hypercholesterolaemia.

The clinical outcome for children and adolescents with homozygous familial hypercholesterolaemia (HoFH) can be devastating, and treatment options are limited in the presence of a null variant. In HoFH, atherosclerotic risk accumulates from birth. Gene therapy is an appealing treatment option as restoration of low-density lipoprotein receptor (LDLR) gene function could provide a cure for HoFH.

Natural History of DNA-Dependent DNA Polymerases: Multiple Pathways to the Origins of DNA.

One of the major evolutionary transitions that led to DNA replacing RNA as the primary informational molecule in biological systems is still the subject of an intense debate in the scientific community. DNA polymerases are currently split into various families. Families A, B, and C are the most significant.

Microsatellite instability assessment is instrumental for Predictive, Preventive and Personalised Medicine: status quo and outlook.

A form of genomic alteration called microsatellite instability (MSI) occurs in a class of tandem repeats (TRs) called microsatellites (MSs) or short tandem repeats (STRs) due to the failure of a post-replicative DNA mismatch repair (MMR) system. Traditionally, the strategies for determining MSI events have been low-throughput procedures that typically require assessment of tumours as well as healthy samples. On the other hand, recent large-scale pan-tumour studies have consistently highlighted the potential of massively parallel sequencing (MPS) on the MSI scale.

Construction and Rescue of a DNA-Launched DENV2 Infectious Clone.

Flaviviruses represent a large group of globally significant, insect-borne pathogens. For many of these viruses, there is a lack of antivirals and vaccines. Thus, there is a need to continue the development of tools to further advance our efforts to combat these pathogens, including reverse genetics techniques.

DNA virome of ticks in the Northeast and Hubei provinces of China reveals diverse single-stranded circular DNA viruses.

Background: Ticks are medically important vectors capable of transmitting a variety of pathogens to and between host species. Although the spectrum of tick-borne RNA viruses has been frequently investigated, the diversity of tick-borne DNA viruses remains largely unknown.

Methods: A total of 1571 ticks were collected from forests and infested animals, and the diversity of the viruses they harbored was profiled using a DNA-specific virome method.

The dual role of DNA repair protein MGMT in cancer prevention and treatment.

Alkylating agents are genotoxic chemicals that can induce and treat various types of cancer. This occurs through covalent bonding with cellular macromolecules, in particular DNA, leading to the loss of functional integrity under the persistence of modifications upon replication. O-alkylguanine (O-AlkylG) adducts are proposed to be the most potent DNA lesions induced by alkylating agents.

A DNA helicase remodeling proteins: How DNA-protein crosslink repair unfolds via FANCJ.

In this issue of Molecular Cell, Yaneva et al. demonstrate that the DNA helicase FANCJ promotes DNA replication-coupled DNA-protein crosslink (DPC) repair via an unexpected ability to unfold the protein adduct, thereby enabling its proteolysis by the DPC protease SPRTN.

A DNA methylation atlas of normal human cell types.

DNA methylation is a fundamental epigenetic mark that governs gene expression and chromatin organization, thus providing a window into cellular identity and developmental processes. Current datasets typically include only a fraction of methylation sites and are often based either on cell lines that underwent massive changes in culture or on tissues containing unspecified mixtures of cells. Here we describe a human methylome atlas, based on deep whole-genome bisulfite sequencing, allowing fragment-level analysis across thousands of unique markers for 39 cell types sorted from 205 healthy tissue samples.

3D chromatin connectivity underlies replication origin efficiency in mouse embryonic stem cells.

In mammalian cells, chromosomal replication starts at thousands of origins at which replisomes are assembled. Replicative stress triggers additional initiation events from 'dormant' origins whose genomic distribution and regulation are not well understood. In this study, we have analyzed origin activity in mouse embryonic stem cells in the absence or presence of mild replicative stress induced by aphidicolin, a DNA polymerase inhibitor, or by deregulation of origin licensing factor CDC6.

ICTV Virus Taxonomy Profile: 2022.

Members of the family are pseudo-spherical and pleomorphic archaeal viruses composed of a membrane vesicle, which encloses a DNA genome. The genome is either circular ssDNA or dsDNA, or linear dsDNA molecules of approximately 7 to 17 kilonucleotides or kbp. Typically, virions contain a single type of transmembrane spike protein at the envelope and a single type of membrane protein, which is embedded in the envelope and located in the internal side of the membrane.

DNA Sequence and Structure under the Prism of Group Theory and Algebraic Surfaces.

Taking a DNA sequence, a word with letters/bases A, T, G and C, as the relation between the generators of an infinite group π, one can discriminate between two important families: (i) the cardinality structure for conjugacy classes of subgroups of π is that of a free group on one to four bases, and the DNA word, viewed as a substitution sequence, is aperiodic; (ii) the cardinality structure for conjugacy classes of subgroups of π is not that of a free group, the sequence is generally not aperiodic and topological properties of π have to be determined differently. The two cases rely on DNA conformations such as A-DNA, B-DNA, Z-DNA, G-quadruplexes, etc. We found a few salient results: Z-DNA, when involved in transcription, replication and regulation in a healthy situation, implies (i).

Evaluation of DNA Methylation Array for Glioma Tumor Profiling and Description of a Novel Epi-Signature to Distinguish IDH1/IDH2 Mutant and Wild-Type Tumors.

Unlabelled: Molecular biomarkers, such as mutations and 1p19q co-deletion, are included in the histopathological and clinical criteria currently used to diagnose and classify gliomas. mutation is a common feature of gliomas and is associated with a glioma-CpG island methylator phenotype (CIMP). Aberrant genomic methylation patterns can also be used to extrapolate information about copy number variation in a tumor.

EbfC/YbaB: A Widely Distributed Nucleoid-Associated Protein in Prokaryotes.

Genomic compaction is an essential characteristic of living organisms. Nucleoid-associated proteins (NAPs) are a group of small proteins that play crucial roles in chromosome architecture and affect DNA replication, transcription, and recombination by imposing topological alterations in genomic DNA, thereby modulating global gene expression. EbfC/YbaB was first described as a DNA-binding protein of that regulates the expression of surface lipoproteins with roles in virulence.

The Complex Roles of DNA Repair Pathways, Inhibitors, Hyperthermia, and Contact Inhibition in Cell Cycle Halts.

The cell cycle has the capacity to safeguard the cell's DNA from damage. Thus, cell cycle arrest can allow tumor cells to investigate their own DNA repair processes. Cancer cells become extremely reliant on G1-phase cyclin-dependent kinases due to mutated oncogenes and deactivated tumor suppressors, producing replication stress and DNA damage during the S phase and destroying checkpoints that facilitate progression through the S/G2/M phase.

Exonucleases: Degrading DNA to Deal with Genome Damage, Cell Death, Inflammation and Cancer.

Although DNA degradation might seem an unwanted event, it is essential in many cellular processes that are key to maintaining genomic stability and cell and organism homeostasis. The capacity to cut out nucleotides one at a time from the end of a DNA chain is present in enzymes called exonucleases. Exonuclease activity might come from enzymes with multiple other functions or specialized enzymes only dedicated to this function.

Cockayne syndrome group B protein uses its DNA translocase activity to promote mitotic DNA synthesis.

Mitotic DNA synthesis, also known as MiDAS, has been suggested to be a form of RAD52-dependent break-induced replication (BIR) that repairs under-replicated DNA regions of the genome in mitosis prior to chromosome segregation. Cockayne syndrome group B (CSB) protein, a chromatin remodeler of the SNF2 family, has been implicated in RAD52-dependent BIR repair of stalled replication forks. However, whether CSB plays a role in MiDAS has not been characterized.

DNA Conformational Changes Induced by Its Interaction with Binuclear Platinum Complexes in Solution Indicate the Molecular Mechanism of Platinum Binding.

Platinum anticancer drugs inhibit the division of cancer cells through a DNA binding mechanism. The bimetallic platinum compounds have a possibility for blocking DNA replication via the cross-linking of DNA functional groups at different distances. Many compounds with metals of the platinum group have been tested for possible antitumor activity.

Distinct structural groups of histone H3 and H4 residues have divergent effects on chronological lifespan in Saccharomyces cerevisiae.

We have performed a comprehensive analysis of the involvement of histone H3 and H4 residues in the regulation of chronological lifespan in yeast and identify four structural groups in the nucleosome that influence lifespan. We also identify residues where substitution with an epigenetic mimic extends lifespan, providing evidence that a simple epigenetic switch, without possible additional background modifications, causes longevity. Residues where substitution result in the most pronounced lifespan extension are all on the exposed face of the nucleosome, with the exception of H3E50, which is present on the lateral surface, between two DNA gyres.

From Metagenomics to Discovery of New Viral Species: Galium Leaf Distortion Virus, a Monopartite Begomovirus Endemic in Mexico.

Begomoviruses (Family ) are a major group of emerging plant viruses worldwide. The knowledge of begomoviruses is mostly restricted to crop plant systems. Nevertheless, it has been described that non-cultivated plants are important reservoirs and vessels of viral evolution that leads to the emergence of new diseases.

Convergence of SIRT1 and ATR signaling to modulate replication origin dormancy.

During routine genome duplication, many potential replication origins remain inactive or 'dormant'. Such origin dormancy is achieved, in part, by an interaction with the metabolic sensor SIRT1 deacetylase. We report here that dormant origins are a group of consistent, pre-determined genomic sequences that are distinguished from baseline (i.

Validation of a DNA methylation microarray for 285,000 CpG sites in the mouse genome.

Mouse has been extensively used as a model organism in many studies to characterize biological pathways and drug effects and to mimic human diseases. Similar DNA sequences between both species facilitate these types of experiments. However, much less is known about the mouse epigenome, particularly for DNA methylation.

PrimPol: A Breakthrough among DNA Replication Enzymes and a Potential New Target for Cancer Therapy.

DNA replication can encounter blocking obstacles, leading to replication stress and genome instability. There are several mechanisms for evading this blockade. One mechanism consists of repriming ahead of the obstacles, creating a new starting point; in humans, PrimPol is responsible for carrying out this task.

LigD: A Structural Guide to the Multi-Tool of Bacterial Non-Homologous End Joining.

DNA double-strand breaks are the most lethal form of damage for living organisms. The non-homologous end joining (NHEJ) pathway can repair these breaks without the use of a DNA template, making it a critical repair mechanism when DNA is not replicating, but also a threat to genome integrity. NHEJ requires proteins to anchor the DNA double-strand break, recruit additional repair proteins, and then depending on the damage at the DNA ends, fill in nucleotide gaps or add or remove phosphate groups before final ligation.