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Cellular and Immunobiology
Published in Karl H. Pang, Nadir I. Osman, James W.F. Catto, Christopher R. Chapple, Basic Urological Sciences, 2021
Masood Moghul, Sarah McClelland, Prabhakar Rajan
Ultraviolet radiation damages DNA by causing cyclobutane pyrimidine dimers and 6‒4 photoproducts lesions on the DNA.Alters DNA structure, impeding correct replication and transcription.Lesions are excised with the recognition, removal, and replacement of the damaged DNA—'nucleotide excision repair'.Base excision repair occurs with localised damage (from free radicals).
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.
Hereditary Colorectal Cancer
Published in Peter Sagar, Andrew G. Hill, Charles H. Knowles, Stefan Post, Willem A. Bemelman, Patricia L. Roberts, Susan Galandiuk, John R.T. Monson, Michael R.B. Keighley, Norman S. Williams, Keighley & Williams’ Surgery of the Anus, Rectum and Colon, 2019
MAP and NAP are syndromes of hereditary adenomatous polyposis due to recessive inheritance of mutations in base excision repair genes, MYH and NTHL1. DNA Base Excision repair is the mechanism by which oxidative damage to the DNA is fixed. Oxidation causes mispairing of the nucleotide base guanine with adenine instead of cytosine. This leads to downstream nucleotide transversions – from GC to TA – causing mutations in daughter cells. The mutations occur in multiple genes, including APC and KRAS. Mutated APC sets up the clinical presentation as mild or attenuated FAP. Mutated KRAS is clinically obvious as serrated polyps.
Molecular radiobiology and the origins of the base excision repair pathway: an historical perspective
Published in International Journal of Radiation Biology, 2023
Ionizing radiation-damaged DNA was a good substrate for endonuclease III, endo VIII and formamidopyrimidine DNA glycosylase as well as a variety of endonucleases that recognize AP sites. Also, E. coli cells mutant in DNA polymerase I or DNA ligase (Paterson et al. 1971; Billen and Hellermann 1976; Zhang et al. 1992), were sensitive to the lethal effects of ionizing radiation. DNA glycosylases, AP endonucleases, repair DNA polymerases and DNA ligases turned out to be the four core enzymes in the Base Excision Repair Pathway (Figure 2), a pathway that evolved primarily to remove endogenous damages resulting from oxidative metabolism, alkylation and heat. However, because of the overlapping spectra of lesions produced by endogenous reactive oxygen species and radiation-induced reactive oxygen species, base excision repair is responsible for removing and repairing the vast majority of ionizing radiation-induced DNA damages.
Targeting the DNA damage response in pediatric malignancies
Published in Expert Review of Anticancer Therapy, 2022
Jenna M Gedminas, Theodore W Laetsch
As opposed to the small base lesions corrected using BER, nucleotide excision repair (NER) removes the bulky DNA lesions caused by UV light, environmental mutagens, and cancer chemotherapy adducts [8]. Once the damage is recognized, transcription factor II H (THFIIH) and XPG are recruited to the site to act as helicases and unwind the DNA. XPG and XPF-ERCC1 then act as endonucleases to cut the DNA on either side of the damage, removing a single strand of 25–30 nucleotides. Proliferating cell nuclear antigen is loaded onto the DNA strand by replication factor C allowing DNA polymerases to copy the undamaged strand. Finally, DNA ligase I and flap endonuclease 1 seal the nicks in the repaired DNA [8]. Poly (ADP-ribose) polymerases (PARPs) are enzymes which play a role in BER and NER, as well as single stranded break repair [9]. PARP binds to sites of DNA strand breaks to facilitate access of the respective repair enzymes to the site [9]. PARP inhibition has shown synthetic lethality with BRCA mutations in the clinical and preclinical setting [9].
MicroRNA Let-7c-5p-Mediated Regulation of ERCC6 Disrupts Autophagic Flux in Age-Related Cataract via the Binding to VCP
Published in Current Eye Research, 2021
Yu Cao, Pengfei Li, Guowei Zhang, Lihua Kang, Tianqiu Zhou, Jian Wu, Yong Wang, Ying Wang, Xiaojuan Chen, Huaijin Guan
Age-related cataract (ARC) is a multifactorial disease that remains the primary cause of irreversible visual impairment and blindness worldwide.1 Genetic and environmental factors are involved in the pathogenesis of ARC.2 UVB exposure causes a burst of reactive oxygen species (ROS) generation in lens tissue and induces structural alterations in DNA, such as the generation of thymine dimers of DNA bases. Oxidative damage to DNA and damage to the DNA repair ability in lens epithelial cells (LECs) are associated with ARC pathogenesis.3–6 Several pathways have been found to be involved in DNA repair, including nucleotide excision repair (NER) and base excision repair (BER).7 NER is a particularly important DNA repair mechanism that removes DNA damage induced by UV.8 During NER, the NER factor is recruited to sites of DNA damage by the Cockayne syndrome complementation group B (CSB) protein (encoded by ERCC6) and then processes the DNA for damage repair. CSB protein deficiency was found to be associated with Cockayne syndrome.9 Our previous research demonstrated that ERCC6 might be epigenetically regulated in LECs in ARC, eventually suppressing the expression of ERCC6.3 Studies have indicated that CSB promotes acetylation of α-tubulin and thereby regulates autophagy.10 However, the role of ERCC6 in the regulation of LECs autophagy remains unknown.