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DNA Repair

Evgeny Kiselev, Thomas S Dexheimer, Christophe Marchand, Shar-Yin Naomi Huang, Yves Pommier
Tyrosyl-DNA phosphodiesterase 1 (TDP1) is an ubiquitous DNA repair enzyme present in yeast, plants and animals. It removes a broad range of blocking lesions at the ends of DNA breaks. The catalytic core of TDP1 consists in a pair of conserved histidine-lysine-asparagine (HKN) motifs. Analysis of the human TDP1 (hTDP1) crystal structure reveals potential involvement of additional residues that shape the substrate binding site. In this biochemical study, we analyzed four such conserved residues, tyrosine 204 (Y204), phenylalanine 259 (F259), serine 400 (S400) and tryptophan 590 (W590)...
May 2, 2018: DNA Repair
Nathaniel W Holton, Yuval Ebenstein, Natalie R Gassman
Environmental exposures, reactive by-products of cellular metabolism, and spontaneous deamination events result in a spectrum of DNA adducts that if un-repaired threaten genomic integrity by inducing mutations, increasing instability, and contributing to the initiation and progression of cancer. Assessment of DNA adducts in cells and tissues is critical for genotoxic and carcinogenic evaluation of chemical exposure and may provide insight into the etiology of cancer. Numerous methods to characterize the formation of DNA adducts and their retention for risk assessment have been developed...
April 27, 2018: DNA Repair
Raima Das, Sharbadeb Kundu, Shaheen Laskar, Yashmin Choudhury, Sankar Kumar Ghosh
Head and neck cancer (HNC), the sixth most common cancer globally, stands second in India. In Northeast (NE) India, it is the sixth most common cause of death in males and seventh in females. Prolonged tobacco and alcohol consumption constitute the major etiological factors for HNC development, which induce DNA damage. Therefore, DNA repair pathway is a crucial system in maintaining genomic integrity and preventing carcinogenesis. The present work was aimed to predict the consequence of significant germline variants of the DNA repair genes in disease predisposition...
April 26, 2018: DNA Repair
Amar Desai, Yan Yan, Stanton L Gerson
The DNA damage response (DDR) is a series of pathways and processes required to repair lesions to DNA. These pathways range from repairing strand breaks to the double helix, damaged bases formed after oxidation or deamination, inaccurate DNA replication resulting in mispaired base alignment, intrastrand crosslinks that trigger cell death, and a plethora of other genomic insults. The DDR is believed to be a critical component of radio and chemoresistance in many cancers as well, with the tumor's ability to repair therapy induced damage being an important tool used to survive traditional chemotherapeutic agents...
April 23, 2018: DNA Repair
Rosario Prados-Carvajal, Ana López-Saavedra, Cristina Cepeda-García, Sonia Jimeno, Pablo Huertas
The appropriate repair of DNA double strand breaks is critical for genome maintenance. Thus, several cellular pathways collaborate to orchestrate a coordinated response. These include the repair of the breaks, which could be achieved by different mechanisms. A key protein involved in the regulation of the repair of broken chromosomes is CtIP. Here, we have found new partners of CtIP involved in the regulation of DNA break repair through affecting DNA end resection. We focus on the splicing complex SF3B and show that its depletion impairs DNA end resection and hampers homologous recombination...
April 22, 2018: DNA Repair
Maryam Majidinia, Saber Ghazizadeh Darband, Mojtaba Kaviani, Seyed Mohammad Nabavi, Rana Jahanban-Esfahlan, Bahman Yousefi
Despite their simple structure, the Notch family of receptors regulates a wide-spectrum of key cellular processes including development, tissue patterning, cell-fate determination, proliferation, differentiation and, cell death. On the other hand, accumulating date pinpointed the role of non-coding microRNAs, namely miRNAs in cancer initiation/progression via regulating the expression of multiple oncogenes and tumor suppressor genes, as such the Notch signaling. It is now documented that these two partners are in one or in the opposite directions and rule together the cancer fate...
April 21, 2018: DNA Repair
Shiladitya Sengupta, Chunying Yang, Muralidhar L Hegde, Pavana M Hegde, Joy Mitra, Arvind Pandey, Arijit Dutta, Abdul Tayyeb Datarwala, Kishor K Bhakat, Sankar Mitra
Posttranslational modifications of DNA repair proteins have been linked to their function. However, it is not clear if posttranslational acetylation affects subcellular localization of these enzymes. Here, we show that the human DNA glycosylase NEIL1, which is involved in repair of both endo- and exogenously generated oxidized bases via the base excision repair (BER) pathway, is acetylated by histone acetyltransferase p300. Acetylation occurs predominantly at Lys residues 296, 297 and 298 located in NEIL1's disordered C-terminal domain...
April 17, 2018: DNA Repair
Deniz Ceylan, Gamze Tuna, Güldal Kirkali, Zeliha Tunca, Güneş Can, Hidayet Ece Arat, Melis Kant, Miral Dizdaroglu, Ayşegül Özerdem
Oxidatively-induced DNA damage has previously been associated with bipolar disorder. More recently, impairments in DNA repair mechanisms have also been reported. We aimed to investigate oxidatively-induced DNA lesions and expression of DNA glycosylases involved in base excision repair in euthymic patients with bipolar disorder compared to healthy individuals. DNA base lesions including both base and nucleoside modifications were measured using gas chromatography-tandem mass spectrometry and liquid chromatography-tandem mass spectrometry with isotope-dilution in DNA samples isolated from leukocytes of euthymic patients with bipolar disorder (n = 32) and healthy individuals (n = 51)...
March 30, 2018: DNA Repair
Yong-Jie Deng, Lei Feng, Huan Zhou, Xiang Xiao, Feng-Ping Wang, Xi-Peng Liu
In cells, degrading DNA and RNA by various nucleases is very important. These processes are strictly controlled and regulated to maintain DNA integrity and to mature or recycle various RNAs. NanoRNase (Nrn) is a 3'-exonuclease that specifically degrades nanoRNAs shorter than 5 nucleotides. Several Nrns have been identified and characterized in bacteria, mainly in Firmicutes. Archaea often grow in extreme environments and might be subjected to more damage to DNA/RNA, so DNA repair and recycling of damaged RNA are very important in archaea...
March 26, 2018: DNA Repair
Jeffrey R Whiteaker, Lei Zhao, Richard G Ivey, Marilyn Sanchez-Bonilla, Heather D Moore, Regine M Schoenherr, Ping Yan, Chenwei Lin, Akiko Shimamura, Amanda G Paulovich
The Fanconi anemia pathway is an important coordinator of DNA repair pathways and is particularly relevant to repair of DNA inter-strand crosslinks. Central to the pathway is monoubiquitination of FANCD2, requiring the function of multiple proteins in an upstream Fanconi core complex. We present development and analytical characterization of a novel assay for quantification of unmodified and monoubiquitinated FANCD2 proteoforms, based on peptide immunoaffinity enrichment and targeted multiple reaction monitoring mass spectrometry (immuno-MRM)...
March 21, 2018: DNA Repair
Eloy Andrés Pérez-Yépez, Héctor Iván Saldívar-Cerón, Olga Villamar-Cruz, Carlos Pérez-Plasencia, Luis Enrique Arias-Romero
p21-activated kinase 1 (PAK1) is a serine/threonine kinase activated by the small GTPases Rac1 and Cdc42. It is located in the chromosome 11q13 and is amplified and/or overexpressed in several human cancer types including 25-30% of breast tumors. This enzyme plays a pivotal role in the control of a number of fundamental cellular processes by phosphorylating its downstream substrates. In addition to its role in the cytoplasm, it is well documented that PAK1 also plays crucial roles in the nucleus participating in mitotic events and gene expression through its association and/or phosphorylation of several transcription factors, transcriptional co-regulators and cell cycle-related proteins, including Aurora kinase A (AURKA), polo-like kinase 1 (PLK1), the forkhead transcription factor (FKHR), estrogen receptor α (ERα), and Snail...
March 21, 2018: DNA Repair
Yuqin Cai, Iwen Fu, Nicholas E Geacintov, Yingkai Zhang, Suse Broyde
How DNA lesions in nucleosomes are recognized for global genome nucleotide excision repair (GG-NER) remains poorly understood, and the roles that histone tails may play remains to be established. Histone H3 and H4 N-terminal tails are of particular interest as their acetylation states are important in regulating nucleosomal functions in transcription, replication and repair. In particular the H3 tail has been the focus of recent attention as a site for the interaction with XPC, the GG-NER lesion recognition factor...
March 8, 2018: DNA Repair
Teresa Morales-Ruiz, Álvaro C Romero-Valenzuela, Vanessa M Vázquez-Grande, Teresa Roldán-Arjona, Rafael R Ariza, Dolores Córdoba-Cañero
Base excision repair (BER) is a major defense pathway against spontaneous DNA damage. This multistep process is initiated by DNA glycosylases that recognise and excise the damaged base, and proceeds by the concerted action of additional proteins that perform incision of the abasic site, gap filling and ligation. BER has been extensively studied in bacteria, yeasts and animals. Although knowledge of this pathway in land plants is increasing, there are no reports detecting BER in algae. We describe here an experimental in vitro system allowing the specific analysis of BER in the model alga Chlamydomonas reinhardtii...
May 2018: DNA Repair
Jinyu Wang, Haitao Zhang, Mohammed Al Shibar, Belinda Willard, Alo Ray, Kurt W Runge
Telomeres, the ends of eukaryotic chromosomes, consist of repetitive DNA sequences and their bound proteins that protect the end from the DNA damage response. Short telomeres with fewer repeats are preferentially elongated by telomerase. Tel1, the yeast homolog of human ATM kinase, is preferentially recruited to short telomeres and Tel1 kinase activity is required for telomere elongation. Rif1, a telomere-binding protein, negatively regulates telomere length by forming a complex with two other telomere binding proteins, Rap1 and Rif2, to block telomerase recruitment...
May 2018: DNA Repair
Pingping Jia, Weihang Chai
Genome instability gives rise to cancer. MLH1, commonly known for its important role in mismatch repair (MMR), DNA damage signaling and double-strand break (DSB) repair, safeguards genome stability. Recently we have reported a novel role of MLH1 in preventing aberrant formation of interstitial telomeric sequences (ITSs) at intra-chromosomal regions. Deficiency in MLH1, in particular its N-terminus, leads to an increase of ITSs. Here, we identify that the ATPase activity in the MLH1 N-terminal domain is important for suppressing the formation of ITSs...
May 2018: DNA Repair
Nidhi Sharma, Srinivas Chakravarthy, Matthew J Longley, William C Copeland, Aishwarya Prakash
The 16.5 kb mitochondrial genome is subjected to damage from reactive oxygen species (ROS) generated in the cell during normal cellular metabolism and external sources such as ionizing radiation and ultraviolet light. ROS cause harmful damage to DNA bases that could result in mutagenesis and various diseases, if not properly repaired. The base excision repair (BER) pathway is the primary pathway involved in maintaining the integrity of mtDNA. Several enzymes that partake in BER within the nucleus have also been identified in the mitochondria...
May 2018: DNA Repair
Carlos H Trasviña-Arenas, Noe Baruch-Torres, Francisco J Cordoba-Andrade, Víctor M Ayala-García, Paola L García-Medel, Corina Díaz-Quezada, Antolín Peralta-Castro, José Juan Ordaz-Ortiz, Luis G Brieba
Plant mitochondrial and chloroplast genomes encode essential proteins for oxidative phosphorylation and photosynthesis. For proper cellular function, plant organelles must ensure genome integrity. Although plant organelles repair damaged DNA using the multi-enzyme Base Excision Repair (BER) pathway, the details of this pathway in plant organelles are largely unknown. The initial enzymatic steps in BER produce a 5'-deoxyribose phosphate (5'-dRP) moiety that must be removed to allow DNA ligation and in plant organelles, the enzymes responsible for the removal of a 5'-dRP group are unknown...
May 2018: DNA Repair
Marketa Tomkova, Michael McClellan, Skirmantas Kriaucionis, Benjamin Schuster-Böckler
No abstract text is available yet for this article.
May 2018: DNA Repair
Paul Jowsey, Nicholas A Morrice, C James Hastie, Hilary MacLauchlan, Rachel Toth, John Rouse
No abstract text is available yet for this article.
May 2018: DNA Repair
Kang-Yi Su, Liang-In Lin, Steven D Goodman, Rong-Syuan Yen, Cho-Yuan Wu, Wei-Chen Chang, Ya-Chien Yang, Wern-Cherng Cheng, Woei-Horng Fang
Deamination of adenine can occur spontaneously under physiological conditions to generate the highly mutagenic lesion, deoxyinosine (hypoxanthine deoxyribonucleotide, dI). In DNA, dI preferably pairs with cytosine rather than thymine and results in A:T to G:C transition mutations after DNA replication. The deamination of adenine is enhanced by ROS from exposure of DNA to ionizing radiation, UV light, nitrous acid, or heat. In Escherichia coli, dI repair is initiated by endonuclease V (endo V; nfi gene product) nicking but a complete repair mechanism has yet to be elucidated...
April 2018: DNA Repair
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