Double Strand Breaks In Dna Essay

With all living organisms, a process known as cell respiration is integral in order to provide the body with an essential form of energy, adenosine triphosphate (ATP). Oxygen, although an essential part of this process, can form reactants from colliding with electrons associated with carrier molecules. (pb101.rcsb.org, 2017). Hydrogen peroxide is an integral product of this reaction but is known to impose negative effects on the body if high levels are introduced. Explicitly, this reaction is caused “If oxygen runs into (one of these) carrier molecules, the electron may be accidentally transferred to it. This converts oxygen into dangerous compounds such as superoxide radicals and hydrogen peroxide, which can attack the delicate sulphur atoms and metal ions in proteins.” (pdbh101.rcb.org, 2017). Research has suggested that the hydrogen peroxide can be converted into hydroxyl radicals, known to mutate DNA, which can potentially cause bodily harm due to DNA’s role in the synthesis of proteins. These radicals can cause detrimental effects on the human body, and studies have suggested a link to ageing. Due to the harmful effects of these H2o2, it is important that the body finds a way to dispose of hydrogen peroxide before concentrations are too great.

The main problem with chromosome instability produced by these breaks is the susceptibility to translocations and thus oncogene activation.

On September 12, 1016, Belmont University graciously allowed Dr. Katherine Friedman from Vanderbilt University to come and talk to a crowd of students about the tendencies of how deoxyribose double stranded breaks can during cell replication and the elements required to hopefully repair this ordeal. She began the session by discussing what chromosomes are composed of and how they are produced, accompanied by visual and statistical representations. Moving on, she touched on how double strand breaks are a huge threat to a cell's, an organisms, stability. Correspondingly, she described what can cause these breaks; chemical factors, as well as inner cell disruptions during replication that are sometimes hard to remedy. However, she also stated that this breaks can occur on purpose, mostly in the immune system in efforts to make antibodies.

The damaged part of the DNA strand is nicked out by endonucleases that contain the dimer, which is then released from the DNA. After the fragment is released, DNA polymerase fills in the gap with a new strand and DNA ligase will close up the repaired strand.

ROS are unstable free radical species which are very reactive. A free radical is a molecule containing one or more unpaired electrons in its outer shell (Pham-Huy et al., 2008). At high concentrations, they are dangerous because they attack biochemical substances, such as fatty acids, protein, carbohydrates and nucleic acids, and cause damage to them (Maes et al., 2011; Valko et al., 2007). This damage causes change in their structure and function. There are three types of ROS, which include the superoxide, hydrogen peroxide and hydroxyl radical (Agarwal et al., 2005). The superoxide is formed during the electron transport chain in the mitochondrion, where electrons from the electron transport chain bind with oxygen to form the superoxide instead of reducing oxygen to water (Valko et al., 2007).

Crossing over in meiosis increases genetic variation in the offspring’s traits. Occurring in interphase one, crossing over is the process

Studies have shown that hydroxyl radical is responsible for oxidative DNA damage. Hydroxyl radicals come from the reaction between ascorbate (vitamin C), uranyl acetate, and hydrogen peroxide as illustrated in scheme 1 . The mechanism of DNA damage begins when the reaction between uranyl acetate and ascorbate (vitamin C) makes plasmid relaxation in pBluescript DNA. pBluescript DNA is a phagemid which includes many advantageous sequences for utilizing cloning with bacteriophage. The rate of DNA strand breaks multiply when the reaction between ascorbate (vitamin C), and uranyl acetate increase. In addition, hydrogen peroxide is the end product when there is a reaction between uranyl ion and ascorbate. DNA damage can happen

In this experiment cells with visible chromosomes were observed in order to find the percent of crossing over during meiosis. Many chromosomes maintain a 4:4 gene ratio but some do truly cross over. The chromosomes that showed a 4:4 ratio as well as the chromosomes that were crossed over were counted and entered into a data table for 2 plates. The map unit and percent of crossover were found using the data collected and also recorded in the chart.

SHM occurs by two mechanisms: 1) DNA replication reads the uracil as a thymidine and pairs it with an adenine which results in a C to T or G to A transition. This type of mutation only requires AID activity68, 69. 2) Uracil is a pyrimidine normally found in RNA and the base-excision repair system will therefore attempt to correct the mistake by removing the uracil. This creates an abasic site in the DNA strand. The removal of the uracil is executed by an enzyme called uracil N-glycosylase (UNG)70, 71. In the abasic site a random nucleotide may be inserted leading to both transitions (G:C into A:T) and transversions (G:C into C:G)68. Ultimately, for both mechanisms it is the misreading of a low fidelity polymerase that is responsible for the introduction of the point mutation72, 73. AID only binds single stranded (ss) DNA and thus only functions on actively transcribed alleles where transcription temporarily separates of the two DNA strands within the transcription bubble74-76. Sequencing studies support this in that mutations only occur downstream of the VH-gene promoter suggesting the importance of this promoter for AID activity. It is hypothesized that AID is recruited

Failure of overcoming such lesions will cause chromosome duplication failure and may lead to mitotic catastrophe, complex chromosomal rearrangements, and tumorigenesis. Multiple mechanisms are developed by the cells to sense and respond to such type of lesions. In replication fork stalling, the cell senses the lesion with replication protein A as well as its downstream factors. At the same time, the Fanconi Anemia proteins facilitates the interstrand crosslinking lesions (see next section, 1.3.2). Particularly, FANCM, together with its binding partners MHFs and FAAP24, will facilitate the activation of ATR/CHK1 signaling pathway for further repair. After proper responses to the replication stresses, the stalled or collapsed replication forks will be restarted (Collis et al., 2008; Wang et al., 2013). Under certain circumstances, single strand DNA gaps will remain on the DNA strand even though the stalled replication forks are successfully overcome, in which a DNA clamp, proliferating cell nuclear antigen (PCNA), and other proteins will function in a postreplication repair to further fix the damages left (Tian et al.,

Werner syndrome is an autosomal recessive genetic condition associated with the WRN gene (7). The WRN gene found on chromosome 8 encodes a protein called Werner (4). The Werner protein works as a helicase assisting in the unwinding of DNA. The helicase belongs to the RecQ helicase family and assists in DNA repair, maintenance and regulation of telomeres (4). The Werner protein also functions as an exonuclease that also assists in DNA repair, replication and transcription (4). The Werner protein has been found to be essential in repairing double stranded breaks during replication fork stalling (3). The WRN gene and Werner protein demonstrate an essential role in the integrity and stability of DNA.

One of the basic consequences of aneuploidy is the genomic instability. Genomic instability refers to the change initiated during the life cycle of a cell. Genetic instability is hallmark of aneuploidy that leads to wide range of changes in the genome of the organisms. These changes can cause serious effects to the organism these include the chromosome alterations, chromosomal mutations. The Structural rearrangements of chromosomes are thought to develop from the repair of double-strand DNA breaks (DSB) by non- homologous end joining (NHEJ) pathway and its variant, alternative NHEJ (also known as backup NHEJ) (Quinlan and Hall, 2012).

In this paper, Bhattacharjee et al. focus on studying both the formation of free radicals and the repair of the resulting DNA damage through the development of methods for accurately creating and identifying DNA damage resulting from free radical reactions. Damage to DNA due to free radical reactions can lead to numerous biological issues both on the molecular level and at the level of the organism’s health, causing issues such as carcinogenesis and cell death. According to Bhattacharjee et al., previously existing methods of quantifying DNA damage were restricted to immunological assays. These assays, however, were limited in the ability to detect DNA damage due to a lack of specificity in antibodies used for the assays as well as an

In humans, three major types of DNA ligases are reported: DNA ligase I (hligI), DNA ligase III (hligIII) and DNA ligase IV (hligIV). hligI plays an important role in DNA replication by joining Okazaki fragments on the lagging strand of DNA. Apart from this it also plays important roles in DNA damage repair pathways, single strand breaks are repaired by nucleotide excision repair (NER) and base excision repair (BER) pathways. Results of preclinical studies support that Human DNA ligases are an attractive target for the development of new anticancer agents for selective inhibition against rapidly proliferating cancer cells. In this mini-review, we will provide a brief discourse of the recently reported human DNA ligase inhibitors as

Double stranded breaks (DSB) occur frequently in eukaryotic cells. It can be caused by many factors such as ultra violet radiation, reactive oxygen species, ionizing radiation et cetera (Lieber,2010). DNA damage leads to rapid growth of tumor leading to cancer. Hence it is very important to repair it before the cell undergoes further division. Two mechanisms of repair system can occur in the cell – homologous recombination (HR) and non homologous DNA end joining (NHEJ). These repair systems along with their mechanism and the repair factors associated with it has been analyzed in this paper. In order for repair factors to access the DNA that are packaged, chromatin remodelers are essential to open the DNA. One way of DNA being