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Double-strand Breaks
DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. A weakened capacity for DNA repair is a risk factor for the development of cancer. DNA is constantly modified in cells, by internal metabolic by-products, and by external ionizing radiation, ultraviolet light, and medicines, resulting in spontaneous DNA damage involving tens of thousands of individual molecular lesions per cell per day. DNA modifications can also be programmed. Molecular lesions can cause structural damage to the DNA molecule, and can alter or eliminate the cell's ability for transcription and gene expression. Other lesions may induce potentially harmful mutations in the cell's genome, which affect the survival of its daughter cells following mitosis. Consequently, DNA repair as part of the DNA damage response (DDR) is constantly active. When normal repair processes fail, including apoptosis, irreparable DNA damage may occ ...
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Cellular Senescence
Cellular senescence is a phenomenon characterized by the cessation of cell division. In their experiments during the early 1960s, Leonard Hayflick and Paul Moorhead found that normal human fetal fibroblasts in culture reach a maximum of approximately 50 cell population doublings before becoming senescent. This process called the Hayflick limit is also known as "replicative senescence", since it is brought about through replication. Hayflick's discovery of mortal cells paved the path for the discovery and understanding of cellular aging molecular pathways. Cellular senescence can be initiated by a wide variety of stress inducing factors. These stress factors include both environmental and internal damaging events, abnormal cellular growth, oxidative stress, autophagy factors, among many other things. The physiological importance for cell senescence has been attributed to prevention of carcinogenesis, and more recently, aging, development, and tissue repair. Senescent cells c ...
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Primary Structure
Protein primary structure is the linear sequence of amino acids in a peptide or protein. By convention, the primary structure of a protein is reported starting from the amino-terminal (N) end to the carboxyl-terminal (C) end. Protein biosynthesis is most commonly performed by ribosomes in cells. Peptides can also be synthesized in the laboratory. Protein primary structures can be directly sequenced, or inferred from DNA sequences. Formation Biological Amino acids are polymerised via peptide bonds to form a long backbone, with the different amino acid side chains protruding along it. In biological systems, proteins are produced during translation by a cell's ribosomes. Some organisms can also make short peptides by non-ribosomal peptide synthesis, which often use amino acids other than the encoded 22, and may be cyclised, modified and cross-linked. Chemical Peptides can be synthesised chemically via a range of laboratory methods. Chemical methods typically synthe ...
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Tumour Heterogeneity
Tumour heterogeneity describes the observation that different tumour cells can show distinct morphological and phenotypic profiles, including cellular morphology, gene expression, metabolism, motility, proliferation, and metastatic potential. This phenomenon occurs both between tumours (inter-tumour heterogeneity) and within tumours (intra-tumour heterogeneity). A minimal level of intra-tumour heterogeneity is a simple consequence of the imperfection of DNA replication: whenever a cell (normal or cancerous) divides, a few mutations are acquired—leading to a diverse population of cancer cells. The heterogeneity of cancer cells introduces significant challenges in designing effective treatment strategies. However, research into understanding and characterizing heterogeneity can allow for a better understanding of the causes and progression of disease. In turn, this has the potential to guide the creation of more refined treatment strategies that incorporate knowledge of heteroge ...
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Tumor Suppressor Gene
A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell (biology), cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results in a loss or reduction in its function. In combination with other genetic mutations, this could allow the cell to grow abnormally. The Loss-of-function mutation, loss of function for these genes may be even more significant in the development of human cancers, compared to the activation of oncogenes. TSGs can be grouped into the following categories: caretaker genes, gatekeeper genes, and more recently landscaper genes. Caretaker genes ensure stability of the genome via DNA repair and subsequently when mutated allow mutations to accumulate. Meanwhile, gatekeeper genes directly regulate cell growth by either inhibiting cell cycle progression or inducing apoptosis. Lastly, landscaper genes regulate growth by contributing to the surrounding e ...
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DNA Damage (naturally Occurring)
Natural 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 brai ...
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Nobel Prize
The Nobel Prizes ( ; ; ) are awards administered by the Nobel Foundation and granted in accordance with the principle of "for the greatest benefit to humankind". The prizes were first awarded in 1901, marking the fifth anniversary of Alfred Nobel, Alfred Nobel's death. The original Nobel Prizes covered five fields: Nobel Prize in Physics, physics, Nobel Prize in Chemistry, chemistry, Nobel Prize in Physiology or Medicine, physiology or medicine, Nobel Prize in Literature, literature, and Nobel Peace Prize, peace, specified in Nobel's will. A sixth prize, the Nobel Memorial Prize in Economic Sciences, Prize in Economic Sciences, was established in 1968 by Sveriges Riksbank (Sweden's central bank) in memory of Alfred Nobel. The Nobel Prizes are widely regarded as the most prestigious awards available in their respective fields.Nobel Prize#Shalev69, Shalev, p. 8. Except in extraordinary circumstances, such as war, all six prizes are given annually. Each recipient, known as a laur ...
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The New York Times
''The New York Times'' (''NYT'') is an American daily newspaper based in New York City. ''The New York Times'' covers domestic, national, and international news, and publishes opinion pieces, investigative reports, and reviews. As one of the longest-running newspapers in the United States, the ''Times'' serves as one of the country's Newspaper of record, newspapers of record. , ''The New York Times'' had 9.13 million total and 8.83 million online subscribers, both by significant margins the List of newspapers in the United States, highest numbers for any newspaper in the United States; the total also included 296,330 print subscribers, making the ''Times'' the second-largest newspaper by print circulation in the United States, following ''The Wall Street Journal'', also based in New York City. ''The New York Times'' is published by the New York Times Company; since 1896, the company has been chaired by the Ochs-Sulzberger family, whose current chairman and the paper's publ ...
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Aziz Sancar
Aziz Sancar (; born 8September 1946) is a Turkish molecular biologist specializing in DNA repair, cell cycle checkpoints, and circadian clock. In 2015, he was awarded the Nobel Prize in Chemistry along with Tomas Lindahl and Paul L. Modrich for their mechanistic studies of DNA repair. He has made contributions on photolyase and nucleotide excision repair in bacteria that have changed his field. Sancar is currently the Sarah Graham Kenan Professor of Biochemistry and Biophysics at the University of North Carolina School of Medicine and a member of the UNC Lineberger Comprehensive Cancer Center. He is the co-founder of the Aziz & Gwen Sancar Foundation, which is a non-profit organization to promote Turkish culture and to support Turkish students in the United States. Early life Aziz Sancar was born on 8 September 1946 to a lower-middle-class family in the Savur district of Mardin Province, southeastern Turkey. His oldest brother Kenan Sancar is a retired brigadier ge ...
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Tomas Lindahl
Tomas Robert Lindahl (born 28 January 1938) is a Swedish-British scientist specialising in cancer research. In 2015, he was awarded the Nobel Prize in Chemistry jointly with American chemist Paul L. Modrich and Turkish chemist Aziz Sancar for mechanistic studies of DNA repair. Education Lindahl was born in Kungsholmen, Stockholm, Sweden to Folke Robert Lindahl and Ethel Hulda Hultberg. He received a PhD degree in 1967, and an MD degree qualification in 1970, from the Karolinska Institutet in Stockholm. Career and research After obtaining his research doctorate, Lindahl did postdoctoral research at Princeton University and Rockefeller University. He was professor of medical chemistry at the University of Gothenburg 1978–82. After moving to the United Kingdom he joined the Imperial Cancer Research Fund (now Cancer Research UK) as a researcher in 1981. From 1986 to 2005 he was the first Director of Cancer Research UK's Clare Hall Laboratories in Hertfordshire, since 20 ...
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Nobel Prize In Chemistry
The Nobel Prize in Chemistry () is awarded annually by the Royal Swedish Academy of Sciences to scientists in the various fields of chemistry. It is one of the five Nobel Prizes established by the will of Alfred Nobel in 1895, awarded for outstanding contributions in chemistry, physics, literature, peace, and physiology or medicine. This award is administered by the Nobel Foundation and awarded by the Royal Swedish Academy of Sciences on proposal of the Nobel Committee for Chemistry, which consists of five members elected by the Academy. The award is presented in Stockholm at an annual ceremony on December 10th, the anniversary of Nobel's death. The first Nobel Prize in Chemistry was awarded in 1901 to Jacobus Henricus van 't Hoff, of the Netherlands, "for his discovery of the laws of chemical dynamics and osmotic pressure in solutions". From 1901 to 2024, the award has been bestowed on a total of 195 individuals. The 2024 Nobel Prize in Chemistry was awarded to Demis Hassabis ...
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Paul Modrich
Paul Lawrence Modrich (born June 13, 1946) is an American biochemist, James B. Duke Professor of Biochemistry at Duke University and Investigator at the Howard Hughes Medical Institute. He is known for his research on DNA mismatch repair. Modrich received the Nobel Prize in Chemistry 2015, jointly with Aziz Sancar and Tomas Lindahl. Early life and education Modrich was born on June 13, 1946, in Raton, New Mexico to Laurence Modrich and Margaret McTurk. He has a younger brother Dave. His father was a biology teacher and coach for basketball, football and tennis at Raton High School where he graduated in 1964. Modrich is of Croatian, Montenegrin, German and Scottish (Gaelic) origin. His paternal grandfather, of Croatian descent, is probably from the small village of Modrići near Zadar, and grandmother of Montenegrin descent, both immigrated to the United States from coastal Croatia in the late 19th century. His maternal family is of mixed German and Scotch-Irish desc ...
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