PARP1
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PARP1
Poly DP-ribosepolymerase 1 (PARP-1) also known as NAD+ ADP-ribosyltransferase 1 or poly DP-ribosesynthase 1 is an enzyme that in humans is encoded by the ''PARP1'' gene. It is the most abundant of the PARP family of enzymes, accounting for 90% of the NAD+ used by the family. PARP1 is mostly present in cell nucleus, but cytosolic fraction of this protein was also reported. Function PARP1 works: * By using NAD+ to synthesize poly ADP ribose (PAR) and transferring PAR moieties to proteins (ADP-ribosylation). * In conjunction with BRCA, which acts on double strands; members of the PARP family act on single strands; or, when BRCA fails, PARP takes over those jobs as well (in a DNA repair context). PARP1 is involved in: * Differentiation, proliferation, and tumor transformation * Normal or abnormal recovery from DNA damage * May be the site of mutation in Fanconi anemia * Induction of inflammation. * The pathophysiology of type I diabetes. PARP1 is activated by: * Helicobacte ...
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ADP-ribosylation
ADP-ribosylation is the addition of one or more ADP-ribose moieties to a protein. It is a reversible post-translational modification that is involved in many cellular processes, including cell signaling, DNA repair, gene regulation and apoptosis. Improper ADP-ribosylation has been implicated in some forms of cancer. It is also the basis for the toxicity of bacterial compounds such as cholera toxin, diphtheria toxin, and others. History The first suggestion of ADP-ribosylation surfaced during the early 1960s. At this time, Pierre Chambon and coworkers observed the incorporation of ATP into hen liver nuclei extract. After extensive studies on the acid insoluble fraction, several different research laboratories were able to identify ADP-ribose, derived from NAD+, as the incorporated group. Several years later, the enzymes responsible for this incorporation were identified and given the name poly(ADP-ribose)polymerase. Originally, this group was thought to be a linear sequence of AD ...
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Poly ADP Ribose Polymerase
Poly (ADP-ribose) polymerase (PARP) is a family of proteins involved in a number of cellular processes such as DNA repair, genomic stability, and programmed cell death. Members of PARP family The PARP family comprises 17 members (10 putative). They vary greatly in structure and function within the cell. * ''PARP1'', '' PARP2'', VPARP (''PARP4''), Tankyrase-1 and -2 (PARP-5a or ''TNKS'', and PARP-5b or ''TNKS2'') have a confirmed PARP activity. * Others include ''PARP3'', , ''TIPARP'' (or "PARP7"), ''PARP8'', , ''PARP10'', , ''PARP12'', , , and ''PARP16 (gene), PARP16''. Structure PARP is composed of four domains of interest: a DNA-binding domain, a caspase-cleaved domain (see below), an auto-modification domain, and a catalytic domain. The DNA-binding domain is composed of two zinc finger structural motif, motifs. In the presence of damaged DNA (base pair-excised), the DNA-binding domain will bind the DNA and induce a Allosteric regulation, conformational shift. It has been ...
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DNA Repair
DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA damage, resulting in tens of thousands of individual molecular lesions per cell per day. Many of these lesions cause structural damage to the DNA molecule and can alter or eliminate the cell's ability to transcribe the gene that the affected DNA encodes. Other lesions induce potentially harmful mutations in the cell's genome, which affect the survival of its daughter cells after it undergoes mitosis. As a consequence, the DNA repair process is constantly active as it responds to damage in the DNA structure. When normal repair processes fail, and when cellular apoptosis does not occur, irreparable DNA damage may occur, including double-strand breaks and DNA crosslinkages (interstrand crosslinks or ICLs). This can eventually lead to malignant ...
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Homologous Recombination
Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (usually DNA as in cellular organisms but may be also RNA in viruses). Homologous recombination is widely used by cells to accurately DNA repair harmful breaks that occur on both strands of DNA, known as double-strand breaks (DSB), in a process called homologous recombinational repair (HRR). Homologous recombination also produces new combinations of DNA sequences during meiosis, the process by which eukaryotes make gamete cells, like sperm and egg cells in animals. These new combinations of DNA represent genetic variation in offspring, which in turn enables populations to adapt during the course of evolution. Homologous recombination is also used in horizontal gene transfer to exchange genetic material between different strains and species of bacteria and viruses. Horizontal ...
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DNA Damage (naturally Occurring)
DNA damage is an alteration in the chemical structure of DNA, such as a break in a strand of DNA, a nucleobase missing from the backbone of DNA, or a chemically changed base such as 8-OHdG. DNA damage can occur naturally or via environmental factors, but is distinctly different from mutation, although both are types of error in DNA. DNA damage is an abnormal chemical structure in DNA, while a mutation is a change in the sequence of base pairs. DNA damages cause changes in the structure of the genetic material and prevents the replication mechanism from functioning and performing properly. The DNA damage response (DDR) is a complex signal transduction pathway which recognizes when DNA is damaged and initiates the cellular response to the damage. DNA damage and mutation have different biological consequences. While most DNA damages can undergo DNA repair, such repair is not 100% efficient. Un-repaired DNA damages accumulate in non-replicating cells, such as cells in the brains o ...
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Chromatin
Chromatin is a complex of DNA and protein found in eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in reinforcing the DNA during cell division, preventing DNA damage, and regulating gene expression and DNA replication. During mitosis and meiosis, chromatin facilitates proper segregation of the chromosomes in anaphase; the characteristic shapes of chromosomes visible during this stage are the result of DNA being coiled into highly condensed chromatin. The primary protein components of chromatin are histones. An octamer of two sets of four histone cores (Histone H2A, Histone H2B, Histone H3, and Histone H4) bind to DNA and function as "anchors" around which the strands are wound.Maeshima, K., Ide, S., & Babokhov, M. (2019). Dynamic chromatin organization without the 30-nm fiber. ''Current opinion in cell biology, 58,'' 95–104. https://doi.o ...
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Nicotinamide Adenine Dinucleotide
Nicotinamide adenine dinucleotide (NAD) is a coenzyme central to metabolism. Found in all living cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an adenine nucleobase and the other nicotinamide. NAD exists in two forms: an oxidized and reduced form, abbreviated as NAD and NADH (H for hydrogen), respectively. In metabolism, nicotinamide adenine dinucleotide is involved in redox reactions, carrying electrons from one reaction to another. The cofactor is, therefore, found in two forms in cells: NAD is an oxidizing agent – it accepts electrons from other molecules and becomes reduced. This reaction, also with H+, forms NADH, which can then be used as a reducing agent to donate electrons. These electron transfer reactions are the main function of NAD. However, it is also used in other cellular processes, most notably as a substrate of enzymes in adding or removing chemical groups to ...
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Microhomology-mediated End Joining
Microhomology-mediated end joining (MMEJ), also known as alternative nonhomologous end-joining (Alt-NHEJ) is one of the pathways for repairing double-strand breaks in DNA. As reviewed by McVey and Lee, the foremost distinguishing property of MMEJ is the use of microhomologous sequences during the alignment of broken ends before joining, thereby resulting in deletions flanking the original break. MMEJ is frequently associated with chromosome abnormalities such as deletions, translocations, inversions and other complex rearrangements. There are multiple pathways for repairing double strand breaks, mainly non-homologous end joining (NHEJ), homologous recombination (HR), and MMEJ. NHEJ directly joins both ends of the double strand break and is relatively accurate, although small (usually less than a few nucleotides) insertions or deletions sometimes occur. HR is highly accurate and uses the sister chromatid as a template for accurate repair of the DSB. MMEJ is distinguished from these ...
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Pun Assay
A pun, also known as paronomasia, is a form of word play that exploits multiple meanings of a term, or of similar-sounding words, for an intended humorous or rhetorical effect. These ambiguities can arise from the intentional use of homophonic, homographic, metonymic, or figurative language. A pun differs from a malapropism in that a malapropism is an incorrect variation on a correct expression, while a pun involves expressions with multiple (correct or fairly reasonable) interpretations. Puns may be regarded as in-jokes or idiomatic constructions, especially as their usage and meaning are usually specific to a particular language or its culture. Puns have a long history in human writing. For example, the Roman playwright Plautus was famous for his puns and word games. Types of puns Homophonic A homophonic pun is one that uses word pairs which sound alike (homophones) but are not synonymous. Walter Redfern summarized this type with his statement, "To pun is to treat homon ...
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In Vivo
Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and plants, as opposed to a tissue extract or dead organism. This is not to be confused with experiments done ''in vitro'' ("within the glass"), i.e., in a laboratory environment using test tubes, Petri dishes, etc. Examples of investigations ''in vivo'' include: the pathogenesis of disease by comparing the effects of bacterial infection with the effects of purified bacterial toxins; the development of non-antibiotics, antiviral drugs, and new drugs generally; and new surgical procedures. Consequently, animal testing and clinical trials are major elements of ''in vivo'' research. ''In vivo'' testing is often employed over ''in vitro'' because it is better suited for observing the overall effects of an experiment on a living subject. In dr ...
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Nucleic Acids Research
''Nucleic Acids Research'' is an open-access peer-reviewed scientific journal published since 1974 by the Oxford University Press. The journal covers research on nucleic acids, such as DNA and RNA, and related work. According to the ''Journal Citation Reports'', the journal's 2021 impact factor is 19.160. The journal publishes two yearly special issues, the first issue of each year is dedicated to biological databases, published in January since 1993, and the other is devoted to papers describing web-based software resources of value to the biological community (web server A web server is computer software and underlying hardware that accepts requests via HTTP (the network protocol created to distribute web content) or its secure variant HTTPS. A user agent, commonly a web browser or web crawler, initiate ...s), published in July since 2003. References External links * * Archives , https://www.ncbi.nlm.nih.gov/pmc/journals/4/ Biochemistry journals Open access j ...
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Replication Fork
In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all living organisms acting as the most essential part for biological inheritance. This is essential for cell division during growth and repair of damaged tissues, while it also ensures that each of the new cells receives its own copy of the DNA. The cell possesses the distinctive property of division, which makes replication of DNA essential. DNA is made up of a double helix of two complementary strands. The double helix describes the appearance of a double-stranded DNA which is thus composed of two linear strands that run opposite to each other and twist together to form. During replication, these strands are separated. Each strand of the original DNA molecule then serves as a template for the production of its counterpart, a process referred to as semiconservative replication. As a result of semi-conservative rep ...
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