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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 cell cycle, or cell-division cycle, is the series of events that take place in a cell that causes it to divide into two daughter cells. These events include the duplication of its DNA and some of its organelles, and subsequently the partitioning of its cytoplasm, chromosomes and other components into two daughter cells in a process called cell division.
In biology, epigenetics is the study of heritable traits, or a stable change of cell function, that happen without changes to the DNA sequence. The Greek prefix epi- in epigenetics implies features that are "on top of" or "in addition to" the traditional genetic mechanism of inheritance. Epigenetics usually involves a change that is not erased by cell division, and affects the regulation of gene expression. Such effects on cellular and physiological phenotypic traits may result from environmental factors, or be part of normal development. They can lead to cancer.
DNA synthesis is the natural or artificial creation of deoxyribonucleic acid (DNA) molecules. DNA is a macromolecule made up of nucleotide units, which are linked by covalent bonds and hydrogen bonds, in a repeating structure. DNA synthesis occurs when these nucleotide units are joined to form DNA; this can occur artificially or naturally. Nucleotide units are made up of a nitrogenous base, pentose sugar (deoxyribose) and phosphate group. Each unit is joined when a covalent bond forms between its phosphate group and the pentose sugar of the next nucleotide, forming a sugar-phosphate backbone. DNA is a complementary, double stranded structure as specific base pairing occurs naturally when hydrogen bonds form between the nucleotide bases.
DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encodes 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. This can eventually lead to malignant tumors, or cancer as per the two-hit hypothesis.
Cockayne syndrome (CS), also called Neill-Dingwall syndrome, is a rare and fatal autosomal recessive neurodegenerative disorder characterized by growth failure, impaired development of the nervous system, abnormal sensitivity to sunlight (photosensitivity), eye disorders and premature aging. Failure to thrive and neurological disorders are criteria for diagnosis, while photosensitivity, hearing loss, eye abnormalities, and cavities are other very common features. Problems with any or all of the internal organs are possible. It is associated with a group of disorders called leukodystrophies, which are conditions characterized by degradation of neurological white matter. There are two primary types of Cockayne syndrome: Cockayne syndrome type A (CSA), arising from mutations in the ERCC8 gene, and Cockayne syndrome type B (CSB), resulting from mutations in the ERCC6 gene.
Nucleotide excision repair is a DNA repair mechanism. DNA damage occurs constantly because of chemicals, radiation and other mutagens. Three excision repair pathways exist to repair single stranded DNA damage: Nucleotide excision repair (NER), base excision repair (BER), and DNA mismatch repair (MMR). While the BER pathway can recognize specific non-bulky lesions in DNA, it can correct only damaged bases that are removed by specific glycosylases. Similarly, the MMR pathway only targets mismatched Watson-Crick base pairs.
ERCC2, or XPD is a protein involved in transcription-coupled nucleotide excision repair.
Transcription factor II H (TFIIH) is an important protein complex, having roles in transcription of various protein-coding genes and DNA nucleotide excision repair (NER) pathways. TFIIH first came to light in 1989 when general transcription factor-δ or basic transcription factor 2 was characterized as an indispensable transcription factor in vitro. This factor was also isolated from yeast and finally named TFIIH in 1992.
Evelyn M. Witkin was an American bacterial geneticist at Cold Spring Harbor Laboratory (1944–1955), SUNY Downstate Medical Center (1955–1971), and Rutgers University (1971–1991). Witkin was considered innovative and inspirational as a scientist, teacher and mentor.
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.
Protein C-ets-1 is a protein that in humans is encoded by the ETS1 gene. The protein encoded by this gene belongs to the ETS family of transcription factors.
DNA excision repair protein ERCC-1 is a protein that in humans is encoded by the ERCC1 gene. Together with ERCC4, ERCC1 forms the ERCC1-XPF enzyme complex that participates in DNA repair and DNA recombination.
Mutation Frequency Decline (mfd) is the gene which encodes the protein Mfd. Mfd functions in transcription-coupled repair to remove a stalled RNA polymerase that has encountered DNA damage and is unable to continue translocating.
M. Ahmad Chaudhry is an American radiologist, Associate Professor at the University of Vermont, and Interim Associate Dean for Research, in the College of Nursing and Health Sciences.
Simon Joseph Boulton is a British scientist who has made important contributions to the understanding of DNA repair and the treatment of cancer resulting from DNA damage. He currently occupies the position of Senior Scientist and group leader of the DSB Repair Metabolism Laboratory at the Francis Crick Institute, London. He is also an honorary Professor at University College London.
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 Polymerase V is a polymerase enzyme involved in DNA repair mechanisms in bacteria, such as Escherichia coli. It is composed of a UmuD' homodimer and a UmuC monomer, forming the UmuD'2C protein complex. It is part of the Y-family of DNA Polymerases, which are capable of performing DNA translesion synthesis (TLS). Translesion polymerases bypass DNA damage lesions during DNA replication - if a lesion is not repaired or bypassed the replication fork can stall and lead to cell death. However, Y polymerases have low sequence fidelity during replication. When the UmuC and UmuD' proteins were initially discovered in E. coli, they were thought to be agents that inhibit faithful DNA replication and caused DNA synthesis to have high mutation rates after exposure to UV-light. The polymerase function of Pol V was not discovered until the late 1990s when UmuC was successfully extracted, consequent experiments unequivocally proved UmuD'2C is a polymerase. This finding lead to the detection of many Pol V orthologs and the discovery of the Y-family of polymerases.
Titia de Lange is the Director of the Anderson Center for Cancer Research, the Leon Hess professor and the head of Laboratory Cell Biology and Genetics at Rockefeller University.
Sir Stephen Philip Jackson, FRS, FMedSci is the Frederick James Quick Professor of Biology. He is a senior group leader at the Cancer Research UK Cambridge Institute and associate group leader at the Gurdon Institute, University of Cambridge.
References
- ↑ "New understanding of DNA repair." Press release, University of Bristol, February 16, 2006. Retrieved January 29, 2010
