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NER pathway

Lang He, Kang Liu, Xiaoshan Wang, Hong Chen, Jin Zhou, Xun Wu, Tao Liu, Yongxue Yang, Xuemei Yang, Dandan Cui, Guiqin Song, Jianguo Lei, Jun Wang
BACKGROUND: Resistance to platinum-based chemotherapy becomes a major obstacle in lung cancer treatment. Compensatory activation of nucleotide excision repair (NER) pathway is the major mechanism accounting for cisplatin-resistance. We aimed at identifying additional regulators in NER-mediated chemoresistance in a hypoxic setting induced by sodium glycididazole (CMNa)-sensitized cisplatin chemotherapy of non-small cell lung cancer (NSCLC). METHODS: We performed an RNA-sequencing (RNA-Seq) analysis to identify the genes whose expression had been differentially regulated in NER-deficient cells that had been treated by cisplatin/CMNa...
May 13, 2018: International Journal of Biochemistry & Cell Biology
Malcolm F White, Thorsten Allers
There has long been a fascination in the DNA Repair pathways of archaea, for two main reasons. Firstly, many archaea inhabit extreme environments where the rate of physical damage to DNA is accelerated. These archaea might reasonably be expected to have particularly robust or novel DNA repair pathways to cope with this. Secondly, the archaea have long been understood to be a lineage distinct from the bacteria, and to share a close relationship with the eukarya, particularly in their information processing systems...
May 5, 2018: FEMS Microbiology Reviews
James R Portman, Terence R Strick
All active living organisms mitigate DNA damage via DNA repair, and the so-called nucleotide excision repair pathway (NER) represents a functionally major part of the cell's DNA repair repertoire [1]. In this pathway, the damaged strand of DNA is incised and removed before being resynthesized. This form of DNA repair requires a multitude of proteins working in a complex choreography. Repair thus typically involves detection of a DNA lesion; validation of that detection event; search for an appropriate incision site and subsequent DNA incision; DNA unwinding/removal; and DNA resynthesis and religation...
May 4, 2018: Journal of Molecular Biology
Yong-Bin Liu, Ying Mei, Zheng-Wen Tian, Jing Long, Chen-Hui Luo, Hong-Hao Zhou
BACKGROUND/AIMS: Rap1 interacting factor 1 (RIF1) was deemed to be involved in replication timing regulation and DNA damage response. However, little is known about the role of RIF1 in malignancies. Thus, this study aimed to investigate whether the expression of RIF1 is relevant to the response of epithelial ovarian cancer (EOC) patients to cisplatin chemotherapy and its underlying mechanism. METHODS: Immunohistochemistry was used for detecting the expression of RIF1 in 72 human ovarian cancer tissues followed by association analysis of RIF1 expression with patients' responses to platinum-based chemotherapy...
April 26, 2018: Cellular Physiology and Biochemistry
Francesco Gentile, Khaled H Barakat, Jack A Tuszynski
The DNA excision repair protein ERCC-1-DNA repair endonuclease XPF (ERCC1-XPF) is a heterodimeric endonuclease essential for the nucleotide excision repair (NER) DNA repair pathway. Although its activity is required to maintain genome integrity in healthy cells, ERCC1-XPF can counteract the effect of DNA-damaging therapies such as platinum-based chemotherapy in cancer cells. Therefore, a promising approach to enhance the effect of these therapies is to combine their use with small molecules, which can inhibit the repair mechanisms in cancer cells...
April 30, 2018: International Journal of Molecular Sciences
Zhiguang Zhao, Anqi Zhang, Yuan Zhao, Junmiao Xiang, Danyang Yu, Zongwen Liang, Chaoyi Xu, Qiong Zhang, Jianmin Li, Ping Duan
Nucleotide excision repair (NER), the core mechanism of DNA repair pathway, was commonly used to maintain genomic stability and prevent tumorigenesis. Previous investigations have demonstrated that single nucleotide polymorphisms (SNPs) of NER pathway genes were associated with various types of cancer. However, there was no research elucidating the genetic association of entire NER pathway with ovarian cancer susceptibility. Therefore, we conducted genotyping for 17 SNPs of six NER core genes (XPA, XPC, XPG, ERCC1, ERCC2 and ERCC4) in 89 ovarian cancer cases and 356 cancer-free controls...
April 18, 2018: Bioscience Reports
Anna Bodzon-Kulakowska, Tereza Padrtova, Anna Drabik, Joanna Ner-Kluza, Anna Antolak, Konrad Kulakowski, Piotr Suder
Morphine is considered a gold standard in pain treatment. Nevertheless, its use could be associated with severe side effects, including drug addiction. Thus, it is very important to understand the molecular mechanism of morphine action in order to develop new methods of pain therapy, or at least to attenuate the side effects of opioids usage. Proteomics allows for the indication of proteins involved in certain biological processes, but the number of items identified in a single study is usually overwhelming...
April 13, 2018: Journal of Proteomics
Palak Shah, Baozhong Zhao, Lei Qiang, Yu-Ying He
Nucleotide excision repair (NER) is the most versatile DNA repair system that removes bulky DNA damage induced by various endogenous and exogenous factors, including UV radiation. Defects in NER can lead to the xeroderma pigmentosum (XP) syndrome, mainly characterized by increased carcinogenesis in the skin. The function of NER factors, including xeroderma pigmentosum group C (XPC), can be regulated by post-translational modifications such as ubiquitination. However, the role of phosphorylation in XPC function remains unknown...
April 6, 2018: Nucleic Acids Research
Robin Eichmiller, Melisa Medina-Rivera, Rachel DeSanto, Eugen Minca, Christopher Kim, Cory Holland, Ja-Hwan Seol, Megan Schmit, Diane Oramus, Jessica Smith, Ignacio F Gallardo, Ilya J Finkelstein, Sang Eun Lee, Jennifer A Surtees
Double strand DNA break repair (DSBR) comprises multiple pathways. A subset of DSBR pathways, including single strand annealing, involve intermediates with 3' non-homologous tails that must be removed to complete repair. In Saccharomyces cerevisiae, Rad1-Rad10 is the structure-specific endonuclease that cleaves the tails in 3' non-homologous tail removal (3' NHTR). Rad1-Rad10 is also an essential component of the nucleotide excision repair (NER) pathway. In both cases, Rad1-Rad10 requires protein partners for recruitment to the relevant DNA intermediate...
April 6, 2018: Nucleic Acids Research
Halh Al-Serori, Franziska Ferk, Michael Kundi, Andrea Bileck, Christopher Gerner, Miroslav Mišík, Armen Nersesyan, Monika Waldherr, Manuel Murbach, Tamara T Lah, Christel Herold-Mende, Andrew R Collins, Siegfried Knasmüller
Some epidemiological studies indicate that the use of mobile phones causes cancer in humans (in particular glioblastomas). It is known that DNA damage plays a key role in malignant transformation; therefore, we investigated the impact of the UMTS signal which is widely used in mobile telecommunications, on DNA stability in ten different human cell lines (six brain derived cell lines, lymphocytes, fibroblasts, liver and buccal tissue derived cells) under conditions relevant for users (SAR 0.25 to 1.00 W/kg)...
2018: PloS One
Aga Syed Sameer, Saniya Nissar
In mammals the bulky DNA adduct lesions known to result in deleterious phenotypes are acted upon and removed from the genomic DNA by nucleotide excision repair (NER) pathway. TFIIH multi-protein complex with its important helicase-Xeroderma Pigmentosum Protein (XPD) serves as the pivotal factor for opening up of the damaged lesion DNA site and carry out the repair process. The initial damage verification step of the TFIIH is in part dependent upon the helicase activity of XPD. Besides, XPD is also actively involved in the initiation steps of transcription and in the regulation of the cell cycle and apoptosis...
2018: Frontiers in Molecular Biosciences
Jing Long, Jun-You Zhu, Yong-Bin Liu, Kun Fu, Yan Tian, Pei-Yao Li, Wen-Qing Yang, Si-Yu Yang, Ji-Ye Yin, Gang Yin, Yu Zhang
OBJECTIVE: To investigate the role of HELQ in chemo-resistance of epithelial ovarian carcinoma (EOC), which is a critical factor of patients' prognosis. METHODS: Immunohistochemistry, survival analysis of our 87 EOC patients and bioinformatics analysis of The Cancer Genome Atlas (TCGA) datasets (Nature, 2011) disclosed the clinical importance of HELQ expression. Quantitative reverse transcription polymerase chain reaction (qRT-PCR), and Western Blot analyses of EOC tissue were used to confirm it...
March 20, 2018: Gynecologic Oncology
Jingwei Liu, Hao Li, Liping Sun, Xue Feng, Zhenning Wang, Yuan Yuan, Chengzhong Xing
Background: Nucleotide excision repair (NER) plays a critical role in maintaining genome integrity. This study aimed to investigate the expression of NER genes and their associations with colorectal cancer (CRC) development. Method: Expressions of NER genes in CRC and normal tissues were analysed by ONCOMINE. The Cancer Genome Atlas (TCGA) data were downloaded to explore relationship of NER expression with clinicopathological parameters and survival of CRC. Results: ERCC1, ERCC2, ERCC5, and DDB2 were upregulated while ERCC4 was downregulated in CRC...
2018: BioMed Research International
Luz I Valenzuela-García, Víctor M Ayala-García, Ana G Regalado-García, Peter Setlow, Mario Pedraza-Reyes
The absence of base excision repair (BER) proteins involved in processing ROS-promoted genetic insults activates a DNA damage scanning (DisA)-dependent checkpoint event in outgrowing Bacillus subtilis spores. Here, we report that genetic disabling of transcription-coupled repair (TCR) or nucleotide excision repair (NER) pathways severely affected outgrowth of ΔdisA spores, and much more so than the effects of these mutations on log phase growth. This defect delayed the first division of spore's nucleoid suggesting that unrepaired lesions affected transcription and/or replication during outgrowth...
March 13, 2018: MicrobiologyOpen
Barbara Bukowska, Boleslaw T Karwowski
The clustered DNA lesions are a characteristic feature of ionizing radiation and are defined as two or more damage sites formed within 20 bps after the passage of a single radiation track. The clustered DNA lesions are divided into two major groups: double-stranded breaks (DSBs) and non-DSB clusters also known as Oxidatively-induced Clustered DNA Lesions (OCDLs), which could involve either two opposing strands or the same strand. As irradiation is gaining greater interest in cancer treatment as well as in imaging techniques, the detailed knowledge of its genotoxicity and the mechanisms of repair of radiation-induced DNA damage remain issues to explore...
February 25, 2018: Current Medicinal Chemistry
Shalaka Chitale, Holger Richly
The integrity of the genome is maintained by specific DNA repair pathways. The main pathway removing DNA lesions induced by exposure to UV light is nucleotide excision repair (NER). The DNA damage response at chromatin is accompanied by the recruitment of DNA repair factors to the lesion site and the deposition of specific histone marks. The function of these histone marks in NER stays for the most part elusive. We have recently reported that the methyltransferase MMSET catalyzes the dimethylation of histone H4 at lysine 20 (H4K20me2) at the lesion site...
January 1, 2018: Nucleus
Marie-Catherine Drigeard Desgarnier, Patrick J Rochette
Absorption of solar ultraviolet (UV) radiation by DNA leads to the formation of the highly mutagenic cyclobutane pyrimidine dimer (CPD). The mutagenicity of CPD is caused, in part, by the fact that their recognition and repair by the nucleotide excision repair (NER) pathway is challenging and slow. It has been previously shown that a pre-stimulation with genotoxic agents improve NER efficiency of CPD, indicating a potential adaptive response of this repair pathway. We have pre-treated human dermal fibroblasts with repeated subletal low doses of UVB (chronic low-dose of UVB; CLUV) to determine whether it could enhance NER capacity to repair CPD...
March 2018: DNA Repair
Yunes Panahi, Amir Fattahi, Hamid Reza Nejabati, Sina Abroon, Zeinab Latifi, Abolfazl Akbarzadeh, Tohid Ghasemnejad
Sulfur mustard (SM) is an alkylating agent that causes severe damages to the skin, eyes, and the respiratory system. DNA alkylation is one of the most critical lesions that could lead to monoadducts and cross-links, as well as DNA strand breaks. In response to these adducts, cells initiate a series of reactions to recruit specific DNA repair pathways. The main DNA repair pathways in human cells, which could be involved in the DNA SM-induced DNA damages, are base excision repair (BER), nucleotide excision repair (NER), homologous recombination (HR) and non-homologous end joining (NHEJ)...
March 2018: Environmental Toxicology and Pharmacology
Lisa N Chesner, Colin Campbell
DNA-protein crosslinks (DPCs) are complex DNA lesions that induce mutagenesis and cell death. DPCs are created by common antitumor drugs, reactive oxygen species, and endogenous aldehydes. Since these agents create other types of DNA damage in addition to DPCs, identification of the mechanisms of DPC repair is challenging. In this study, we created plasmid substrates containing site-specific DPC lesions, as well as plasmids harboring lesions that are selectively repaired by the base excision or nucleotide excision repair (NER) pathways...
February 2018: DNA Repair
Janin Lehmann, Christina Seebode, Marie Christine Martens, Steffen Emmert
Ultraviolet (UV)-induced DNA lesions are almost exclusively removed by the nucleotide excision repair (NER) pathway, which is essential for prevention of skin cancer development. Patients with xeroderma pigmentosum (XP) are extremely sun sensitive due to a genetic defect in components of the NER cascade. They present with first signs of premature skin aging at an early age, with a considerably increased risk of developing UV-induced skin cancer. XP belongs to the group of DNA repair defective disorders that are mainly diagnosed in the clinic and in hindsight confirmed at the molecular level...
February 2018: Anticancer Research
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