China
Africa
Explore chapters and articles related to this topic
Mitochondrial Genome Damage, Dysfunction and Repair
Published in Shamim I. Ahmad, Handbook of Mitochondrial Dysfunction, 2019
Kalyan Mahapatra, Sayanti De, Sujit Roy
Mitochondrial BER pathway follows similar three-step mechanism like that of seen in nuclear BER pathway, i.e., recognition and elimination of damaged base, gap tailoring and DNA synthesis/ligation. Depending on the DNA polymerase mediated insertion of either single nucleotide or short sequence, BER pathway is of two types, i.e., short-patch BER and long-patch BER. Although animal mitochondria show both of them, plant mitochondria are restricted to short-patch BER only (Mecocci et al., 1993).The first step in Short patch BER is recognition of the damaged base and its elimination. The damaged base is recognized by two types of DNA glycosylase i.e., monofunctional and bifunctional.
DNA Repair During Aging
Published in Alvaro Macieira-Coelho, Molecular Basis of Aging, 2017
This is a repair pathway based on the action of glycosylases. A DNA glycosylase catalyzes the hydrolysis of the N-glycosylic bonds linking bases to the deoxyribose-phosphate backbone, leaving a base-free site (AP site). The removal of such a site requires the action of an AP endonuclease that incises the DNA. Many such enzymes have been characterized in mammals.43 They remove uracil, hypoxanthine, 3-methyladenine, 7-methylguanine, urea, hydroxymethyluracil, and thymine-glycol in different organs of the mouse, rat, calf, and humans. An AP site formed by these enzymes can be removed by the sequential action of a 5′-acting and a 3′-acting AP endonuclease. The resulting gap is enlarged by the action of an exonuclease in both directions that is not specifically repair directed. The gap is filled in by a polymerase and the last nick ligated. Some of these enzymes exhibit both a glycosylase and an AP endonuclease activity, especially those that remove bases damaged by oxidation.
Target Amplification-Based Techniques
Published in Attila Lorincz, Nucleic Acid Testing for Human Disease, 2016
Antoinette A.T.P. Brink, Peter J.F. Snijders, Chris J.L.M. Meijer
Uracil DNA glycosylase (UDG) cleaves the uracil from the phosphodiester backbone of uracil-containing DNA. The resulting apyrimidinic sites block replication by DNA polymerases and are very labile to acid–base hydrolysis. UDG does not react with free deoxyuridine 5-triphosphate (dUTP) and is inactivated by heat denaturation. These properties can be utilized to prevent reaction product carry-over by incorporating dUTP in all PCR products (by substituting dUTP for dTTP or by incorporating uracil during primer synthesis) and treating all subsequent preassembled reactions with UDG, followed by heat-denaturation of UDG.39 UDG is commercially available (e.g., AmpErase from Applied Biosystems) and is used in many diagnostic laboratories.
A novel polymerase β inhibitor from phage displayed peptide library augments the anti-tumour effects of temozolomide on colorectal cancer
Published in Journal of Chemotherapy, 2022
Lihong Qin, Mao Huiwen, Jianguo Wang, Yuanyaun Wang, Salman A. Khan, Ying Zhang, Hong Qiu, Longwei Jiang, Lingfeng He, Yan Zhang, Shaochang Jia
Growing studies reveal that DNA repair pathways enable tumour cells to survive DNA damage induced by chemotherapeutic drugs [13]. BER is recognized as the predominant DNA repair pathway for eliminating small DNA base lesions in mammalian cells [14, 15]. Damaged base residues are removed by alkyladenine DNA glycosylase (Aag), a lesion-specific DNA glycosylase. Next the resulting abasic site is recognized by APE1 (an apurinic/apyrimidinic endonuclease) to incise the damaged strand, leaving 5 V deoxyribose phosphate (5’dRP) and 3’OH group at the margin. A DNA polymerase β (pol-β)–mediated DNA synthesis step fills the single nucleotide gap, and the 5’dRP lyase activity of pol-β, removes the cytotoxic 5’dRP group. Subsequent reactions are coordinated by PARP1 and/or XRCC1 with Pol β and DNA ligase completing the repair pathway. [16–18].
The use of a 2-aminopurine-containing split G-quadruplex for sequence-specific DNA detection
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Sung Hyun Hwang, Woo Young Kwon, Hyunmin Eun, Sehan Jeong, Jun Seok Park, Kwang Jin Kim, Hyung Joo Kim, Sang Hyun Lee, Kyungmoon Park, Jeong-Jun Yoon, Yung-Hun Yang, Ki Soo Park
It is known that incorporation of 2-AP into G-rich sequences results in fluorescence enhancement to a level, which is comparable to that of free 2-AP, owing to formation of a G-quadruplex, a structure formed by stacking complexes comprised of four guanine bases linked via Hoogsteen hydrogen bonding [12–21]. It is assumed that π stacking within the loops of the G-quadruplex is distorted and, thus, that electron transfer quenching of 2-AP by guanine does not effectively occur. As a result, 2-AP in this environment displays strong fluorescence like it does in its free state. Owing to the improved fluorescence properties, 2-AP incorporated in a G-quadruplex has been widely used as a key component in various biosensing platforms, for the detection of various target molecules including metal ions, microRNA, and proteins [19,21,22]. For example, Lee et al. devised a uracil DNA glycosylase (UDG) activity assay, which relies on the formation of 2-AP-incorporated G-quadruplex in response to UDG. Overall, these 2-AP-based approaches overcome the limitations of alternative approaches that require expensive and time-consuming modifications of both a fluorophore and quencher [19–21].
Development and implementation of precision therapies targeting base-excision DNA repair in BRCA1-associated tumors
Published in Expert Review of Precision Medicine and Drug Development, 2019
Adel Alblihy, Katia A. Mesquita, Maaz T. Sadiq, Srinivasan Madhusudan
Base excision repair (BER) is a vital pathway by which an inappropriate base is recognized and incised. An inappropriate base can be originated by oxidation, alkylation, single strand break, ring saturation, and base deamination mechanism [62]. DNA glycosylases are enzymes that excise the damaged base and catalyze the hydrolysis of the N-glycosylic bond. This process leads to an abasic site (AP) with an intact DNA phosphodiester backbone [63]. Some glycosylases such as the endonuclease VIII-like protein (NEIL1) and 8-oxoguanine glycosylase (OGG1) have dual functions (Figure 2). They can also incise the DNA phosphodiester backbone to create a single 3ʹ-strand in the AP site [64]