This variation in binding strength along the DNA yields intrinsic differences in the accessibility of different DNA regions within NCPs. The H3 αN helix specifically interacts with the ends of the NCP DNA, and thus plays an important role in regulating NCP DNA unwrapping (see below). The H3–H4 tetramer strongly interacts with the central ~60 bp of NCP DNA, while the H2A–H2B dimers interact more weakly with the flanking ~30 bp of NCP DNA. These contacts are mainly electrostatic, where the minor groove of DNA interacts primarily with ‘sprocket’ arginine residues at regular ~ 10 bp intervals on each side of the pseudo-two-fold dyad axis of symmetry ( 5, 6). Positioning of histone octamers on DNA is greatly influenced by histone–DNA interactions in the NCP ( 4). In addition, histone variants (primarily of histones H2A and H3) are present in subsets of nucleosomes, and play important roles in specific chromatin functions ( 3). In the octameric complex, histones H3 and H4 form a tetramer that is flanked by two dimers of histones H2A and H2B. The NCP contains an octamer of the well-conserved core histones H2A, H2B, H3, and H4, and ~147 bp of DNA coiled in ~1.7 left-handed turns around the wedge-shaped histone octamer surface ( 2). NCPs and linker DNA are often complexed with linker histones (H1 and associated variants), which promote compaction of the nucleosome arrays into chromatin fibers. The basic repeating unit of chromatin fibers, the nucleosome, consists of the nucleosome core particle (NCP) and varying lengths of ‘linker DNA’ (from 20 bp to >100 bp, depending on the organism) stretching between these units ( 1).
In all eukaryotic cells, chromatin fibers are heterogeneous and dynamic. For brevity, we refer the reader to reviews wherever possible, which contain the seminal references for specific concepts. In this report, we review the historical development of our current understanding of UV-induced DNA damage in chromatin, and highlight recent developments exploring DNA damage and repair in chromatin at the genome-wide level.
Element 3d v2.2 unwrap uvw skin#
UV radiation is a ubiquitous threat to the genomes of essentially all terrestrial organisms and the etiological agent underlying the development of several hereditary diseases and skin cancers. A prototype environmental agent used extensively in studies examining DNA damage and repair in chromatin has been ultraviolet (UV) radiation. Understanding variations in the distribution of DNA damage and repair in chromatin, together with their effects on chromatin structure, are crucial features of genomic instability. It has long been recognized that the target of DNA damaging agents and the ‘landscape’ of DNA repair enzymes in eukaryotes is the compact and dynamic structure of chromatin. Finally, we discuss our current understanding of how the distribution and repair of UV-induced DNA damage influence mutagenesis in human skin cancers. We also describe recent progress in genome-wide methods for mapping UV damage, which echoes early biochemical studies, and highlights the role of nucleosomes and transcription factors in UV damage formation and repair at unprecedented resolution. We describe the initial discovery that nucleosomes and other DNA-binding proteins induce characteristic ‘photofootprints’ during the formation of UV photoproducts. Here, we review how chromatin impacts the formation of UV photoproducts in eukaryotic cells. In eukaryotes, both the formation and repair of UV damage occur in the context of chromatin, in which genomic DNA is packaged with histones into nucleosomes and higher-order chromatin structures. Other: Includes any assessment tools that do not logically fit into the above categories.UV radiation induces photolesions that distort the DNA double helix and, if not repaired, can cause severe biological consequences, including mutagenesis or cell death. Final environment and character renderingsĮxams: All forms of formal testing, other than skill performance exams. Modeling, texturing and rigging projects environment models. Skill Demonstrations: All skill-based and physical demonstrations used for assessment purposes including skill performance exams. Problem solving: Assessment tools, other than exams, that demonstrate competence in computational or non-computational problem solving skills.
This is a degree applicable course but assessment tools based on writing are not included because problem solving assessments and skill demonstrations are more appropriate for this course. Writing: Assessment tools that demonstrate writing skill and/or require students to select, organize and explain ideas in writing.