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DNA Repair

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https://www.readbyqxmd.com/read/28903076/role-of-human-dna2-hdna2-as-a-potential-target-for-cancer-and-other-diseases-a-systematic-review
#1
REVIEW
Pan-Pan Jia, Muhammad Junaid, Yan-Bo Ma, Farooq Ahmad, Yong-Fang Jia, Wei-Guo Li, De-Sheng Pei
DNA nuclease/helicase 2 (DNA2), a multi-functional protein protecting the high fidelity of genomic transmission, plays critical roles in DNA replication and repair processes. In the maturation of Okazaki fragments, DNA2 acts synergistically with other enzymes to cleave the DNA-RNA primer flaps via different pathways. DNA2 is also involved in the stability of mitochondrial DNA and the maintenance of telomeres. Moreover, DNA2 potentially participates in controlling the cell cycle by repairing the DNA replication faults at main checkpoints...
September 6, 2017: DNA Repair
https://www.readbyqxmd.com/read/28892740/human-ogg1-activity-in-nucleosomes-is-facilitated-by-transient-unwrapping-of-dna-and-is-influenced-by-the-local-histone-environment
#2
Katharina Bilotti, Erin E Kennedy, Chuxuan Li, Sarah Delaney
If unrepaired, damage to genomic DNA can cause mutations and/or be cytotoxic. Single base lesions are repaired via the base excision repair (BER) pathway. The first step in BER is the recognition and removal of the nucleobase lesion by a glycosylase enzyme. For example, human oxoguanine glycosylase 1 (hOGG1) is responsible for removal of the prototypic oxidatively damaged nucleobase, 8-oxo-7,8-dihydroguanine (8-oxoG). To date, most studies of glycosylases have used free duplex DNA substrates. However, cellular DNA is packaged as repeating nucleosome units, with 145 base pair segments of DNA wrapped around histone protein octamers...
September 1, 2017: DNA Repair
https://www.readbyqxmd.com/read/28866241/acylpeptide-hydrolase-is-a-component-of-the-cellular-response-to-dna-damage
#3
Zhihong Zeng, Stuart L Rulten, Claire Breslin, Anastasia Zlatanou, Victoria Coulthard, Keith W Caldecott
Acylpeptide hydrolase (APEH) deacetylates N-alpha-acetylated peptides and selectively degrades oxidised proteins, but the biochemical pathways that are regulated by this protease are unknown. Here, we identify APEH as a component of the cellular response to DNA damage. Although APEH is primarily localised in the cytoplasm, we show that a sub-fraction of this enzyme is sequestered at sites of nuclear damage following UVA irradiation or following oxidative stress. We show that localization of APEH at sites of nuclear damage is mediated by direct interaction with XRCC1, a scaffold protein that accelerates the repair of DNA single-strand breaks...
August 24, 2017: DNA Repair
https://www.readbyqxmd.com/read/28863396/proximity-effects-in-chromosome-aberration-induction-by-low-let-ionizing-radiation
#4
John James Tello Cajiao, Mario Pietro Carante, Mario Antonio Bernal Rodriguez, Francesca Ballarini
Although chromosome aberrations are known to derive from distance-dependent mis-rejoining of chromosome fragments, evaluating whether a certain model describes such "proximity effects" better than another one is complicated by the fact that different approaches have often been tested under different conditions. Herein, a biophysical model ("BIANCA", i.e. BIophysical ANalysis of Cell death and chromosome Aberrations) was upgraded, implementing explicit chromosome-arm domains and two new models for the dependence of the rejoining probability on the fragment initial distance, r...
August 24, 2017: DNA Repair
https://www.readbyqxmd.com/read/28846868/transcription-coupled-repair-deficiency-protects-against-human-mutagenesis-and-carcinogenesis-personal-reflections-on-the-50th-anniversary-of-the-discovery-of-xeroderma-pigmentosum
#5
REVIEW
James E Cleaver
Xeroderma pigmentosum (XP) patients who lack the main damage recognition protein for global genome repair (GGR), XPC, have greatly increased skin cancer rates and elevated mutation frequencies originating from unrepaired ultraviolet photoproducts in the nontranscribed regions of the genome and in nontranscribed strands of expressed genes. But they show no increased mutations in transcribed strands. In contrast, cancer is absent from Cockayne syndrome (CS) patients that have defective transcription coupled repair (TCR) despite severe photosensitivity, CS patients remarkably show no elevation of UV induced mutagenesis implying that defective TCR may be protective against mutagenesis and carcinogenesis...
August 23, 2017: DNA Repair
https://www.readbyqxmd.com/read/28865289/dna-polymerase-%C3%AE-the-long-and-the-short-of-it
#6
Ekaterina G Frank, Mary P McLenigan, John P McDonald, Donald Huston, Samantha Mead, Roger Woodgate
The cDNA encoding human DNA polymerase ι (POLI) was cloned in 1999. At that time, it was believed that the POLI gene encoded a protein of 715 amino acids. Advances in DNA sequencing technologies led to the realization that there is an upstream, in-frame initiation codon that would encode a DNA polymerase ι (polι) protein of 740 amino acids. The extra 25 amino acid region is rich in acidic residues (11/25) and is reasonably conserved in eukaryotes ranging from fish to humans. As a consequence, the curated Reference Sequence (RefSeq) database identified polι as a 740 amino acid protein...
August 19, 2017: DNA Repair
https://www.readbyqxmd.com/read/28846869/xlf-cernunnos-an-important-but-puzzling-participant-in-the-nonhomologous-end-joining-dna-repair-pathway
#7
REVIEW
Vijay Menon, Lawrence F Povirk
DNA double strand breaks (DSBs) are one of the most deleterious DNA lesions that promote cell death, genomic instability and carcinogenesis. The two major cellular mechanisms that repair DSBs are Nonhomologous End-Joining (NHEJ) and Homologous Recombination Repair (HRR). NHEJ is the predominant pathway, in which XLF (also called Cernunnos) is a key player. Patients with XLF mutation exhibit microcephaly, lymphopenia, and growth retardation, and are immunodeficient and radiosensitive. During NHEJ, XLF interacts with XRCC4-Ligase IV, stimulates its ligase activity, and forms DNA-binding filaments of alternating XLF and XRCC4 dimers that may serve to align broken DNA and promote ligation of noncomplementary ends...
August 18, 2017: DNA Repair
https://www.readbyqxmd.com/read/28843610/role-of-the-dna-repair-glycosylase-ogg1-in-the-activation-of-murine-splenocytes
#8
Marco Seifermann, Alexander Ulges, Tobias Bopp, Svetlana Melcea, Andrea Schäfer, Sugako Oka, Yusaku Nakabeppu, Arne Klungland, Christof Niehrs, Bernd Epe
OGG1 (8-oxoguanine-DNA glycosylase) is the major DNA repair glycosylase removing the premutagenic DNA base modification 8-oxo-7,8-dihydroguanine (8-oxoG) from the genome of mammalian cells. In addition, there is accumulating evidence that OGG1 and its substrate 8-oxoG might function in the regulation of certain genes, which could account for an attenuated immune response observed in Ogg1(-/-) mice in several settings. Indications for at least two different mechanisms have been obtained. Thus, OGG1 could either act as an ancillary transcription factor cooperating with the lysine-specific demethylase LSD1 or as an activator of small GTPases...
August 12, 2017: DNA Repair
https://www.readbyqxmd.com/read/28837865/valproic-acid-sensitizes-breast-cancer-cells-to-hydroxyurea-through-inhibiting-rpa2-hyperphosphorylation-mediated-dna-repair-pathway
#9
Youjia Tian, Guochao Liu, Hui Wang, Zhujun Tian, Zuchao Cai, Fengmei Zhang, Yue Luo, Shue Wang, Gongshe Guo, Xiaowei Wang, Simon Powell, Zhihui Feng
It was reported that valproic acid (VPA, a histone deacetylase inhibitor) can sensitize cancer cells to hydroxyurea (HU, a ribonucleotide reductase inhibitor) for chemotherapy, although the mechanism of VPA-induced HU sensitization is unclear. In this study, we systematically characterized VPA-induced HU sensitization of breast cancer cells. Multiple breast cancer cell models were employed to investigate whether the safe concentration of 0.5mM VPA and 2mM HU can result in DNA double-strand breaks (DSBs) and impact cell survival...
August 9, 2017: DNA Repair
https://www.readbyqxmd.com/read/28822913/polyphosphate-is-a-key-factor-for-cell-survival-after-dna-damage-in-eukaryotic-cells
#10
Samuel Bru, Bàrbara Samper-Martín, Eva Quandt, Sara Hernández-Ortega, Joan M Martínez-Laínez, Eloi Garí, Marta Rafel, Javier Torres-Torronteras, Ramón Martí, Mariana P C Ribeiro, Javier Jiménez, Josep Clotet
Cells require extra amounts of dNTPs to repair DNA after damage. Polyphosphate (polyP) is an evolutionary conserved linear polymer of up to several hundred inorganic phosphate (Pi) residues that is involved in many functions, including Pi storage. In the present article, we report on findings demonstrating that polyP functions as a source of Pi when required to sustain the dNTP increment essential for DNA repair after damage. We show that mutant yeast cells without polyP produce less dNTPs upon DNA damage and that their survival is compromised...
August 8, 2017: DNA Repair
https://www.readbyqxmd.com/read/28800560/molecular-basis-for-the-functions-of-a-bacterial-muts2-in-dna-repair-and-recombination
#11
Ge Wang, Robert J Maier
Bacterial MutS2 proteins, consisting of functional domains for ATPase, DNA-binding, and nuclease activities, play roles in DNA recombination and repair. Here we observe a mechanism for generating MutS2 expression diversity in the human pathogen Helicobacter pylori, and identify a unique MutS2 domain responsible for specific DNA-binding. H. pylori strains differ in mutS2 expression due to variations in the DNA upstream sequence containing short sequence repeats. Based on Western blots, mutS2 in some strains appears to be co-translated with the upstream gene, but in other strains (e...
July 19, 2017: DNA Repair
https://www.readbyqxmd.com/read/28738244/dna-binding-and-unwinding-by-hel308-helicase-requires-dual-functions-of-a-winged-helix-domain
#12
Sarah J Northall, Ryan Buckley, Nathan Jones, J Carlos Penedo, Panos Soultanas, Edward L Bolt
Hel308 helicases promote genome stability linked to DNA replication in archaea, and have homologues in metazoans. In the crystal structure of archaeal Hel308 bound to a tailed DNA duplex, core helicase domains encircle single-stranded DNA (ssDNA) in a "ratchet" for directional translocation. A winged helix domain (WHD) is also present, but its function is mysterious. We investigated the WHD in full-length Hel308, identifying that mutations in a solvent exposed α-helix resulted in reduced DNA binding and unwinding activities...
July 16, 2017: DNA Repair
https://www.readbyqxmd.com/read/28732309/zebularine-induces-replication-dependent-double-strand-breaks-which-are-preferentially-repaired-by-homologous-recombination
#13
Manuel Luis Orta, Nuria Pastor, Estefanía Burgos-Morón, Inmaculada Domínguez, José Manuel Calderón-Montaño, Carlos Huertas Castaño, Miguel López-Lázaro, Thomas Helleday, Santiago Mateos
Zebularine is a second-generation, highly stable hydrophilic inhibitor of DNA methylation with oral bioavailability that preferentially target cancer cells. It acts primarily as a trap for DNA methyl transferases (DNMTs) protein by forming covalent complexes between DNMT protein and zebularine-substrate DNA. It's well documented that replication-blocking DNA lesions can cause replication fork collapse and thereby to the formation of DNA double-strand breaks (DSB). DSB are dangerous lesions that can lead to potentially oncogenic genomic rearrangements or cell death...
July 12, 2017: DNA Repair
https://www.readbyqxmd.com/read/28704715/differential-effect-of-the-overexpression-of-rad2-xpg-family-endonucleases-on-genome-integrity-in-yeast-and-human-cells
#14
Sonia Jimeno, Emilia Herrera-Moyano, Pedro Ortega, Andrés Aguilera
Eukaryotic cells possess several DNA endonucleases that are necessary to complete different steps in DNA metabolism. Rad2/XPG and Rad27/FEN1 belong to a group of evolutionary conserved proteins that constitute the Rad2 family. Given the important roles carried out by these nucleases in DNA repair and their capacity to create DNA breaks, we have investigated the effect that in vivo imbalance of these nucleases and others of the family have on genome integrity and cell proliferation. We show that overexpression of these nucleases causes genetic instability in both yeast and human cells...
July 3, 2017: DNA Repair
https://www.readbyqxmd.com/read/28704716/transcriptional-consequences-of-xpa-disruption-in-human-cell-lines
#15
Mandira Manandhar, Megan G Lowery, Karen S Boulware, Kevin H Lin, Yue Lu, Richard D Wood
Nucleotide excision repair (NER) in mammalian cells requires the xeroderma pigmentosum group A protein (XPA) as a core factor. Remarkably, XPA and other NER proteins have been detected by chromatin immunoprecipitation at some active promoters, and NER deficiency is reported to influence the activated transcription of selected genes. However, the global influence of XPA on transcription in human cells has not been determined. We analyzed the human transcriptome by RNA sequencing (RNA-Seq). We first confirmed that XPA is confined to the cell nucleus even in the absence of external DNA damage, in contrast to previous reports that XPA is normally resident in the cytoplasm and is imported following DNA damage...
June 29, 2017: DNA Repair
https://www.readbyqxmd.com/read/28689072/nucleolytic-degradation-of-3-ending-overhangs-is-essential-for-dna-end-resection-in-reca-loading-deficient-recb-mutants-of-escherichia-coli
#16
Siniša Ivanković, Dušica Vujaklija, Damir Đermić
Degradation of a 5'-ending strand is the hallmark of the universal process of DNA double strand break (DSB) resection, which results in creation of the central recombination intermediate, a 3'-ending overhang. Here we show that in Escherichia coli recB1080/recB1067 mutants, which are devoid of RecBCD's nuclease and RecA loading activities, degradation of the unwound 3' tail is as essential as is degradation of its 5'-ending complement. Namely, a synergistic action of ExoI, ExoVII, SbcCD and ExoX single-strand specific exonucleases (ssExos) of 3'-5' polarity was essential for preserving cell viability, DNA repair and homologous recombination in the recB1080/recB1067 mutants, to the same extent as the redundant action of 5'-tail trimming ssExos RecJ and ExoVII...
June 27, 2017: DNA Repair
https://www.readbyqxmd.com/read/28783563/stimulation-of-rna-polymerase-ii-ubiquitination-and-degradation-by-yeast-mrna-3-end-processing-factors-is-a-conserved-dna-damage-response-in-eukaryotes
#17
Jason N Kuehner, James W Kaufman, Claire Moore
The quality and retrieval of genetic information is imperative to the survival and reproduction of all living cells. Ultraviolet (UV) light induces lesions that obstruct DNA access during transcription, replication, and repair. Failure to remove UV-induced lesions can abrogate gene expression and cell division, resulting in permanent DNA mutations. To defend against UV damage, cells utilize transcription-coupled nucleotide excision repair (TC-NER) to quickly target lesions within active genes. In cases of long-term genotoxic stress, a slower alternative pathway promotes degradation of RNA Polymerase II (Pol II) to allow for global genomic nucleotide excision repair (GG-NER)...
September 2017: DNA Repair
https://www.readbyqxmd.com/read/28779964/the-c-elegans-set-2-set1-histone-h3-lys4-h3k4-methyltransferase-preserves-genome-stability-in-the-germline
#18
M Herbette, M G Mercier, F Michal, D Cluet, C Burny, G Yvert, V J Robert, F Palladino
Maintaining the integrity of genetic information across generations is essential for both cell survival and reproduction, and requires the timely repair of DNA damage. Histone-modifying enzymes play a central role in the DNA repair process through the deposition and removal of post-translational modifications on the histone tails. Specific histone modification act in the DNA repair process through the recruitment of proteins and complexes with specific enzymatic activities, or by altering the chromatin state at the site of DNA lesions...
September 2017: DNA Repair
https://www.readbyqxmd.com/read/28759779/synthetic-lethality-between-murine-dna-repair-factors-xlf-and-dna-pkcs-is-rescued-by-inactivation-of-ku70
#19
Mengtan Xing, Magnar Bjørås, Jeremy A Daniel, Frederick W Alt, Valentyn Oksenych
DNA double-strand breaks (DSBs) are recognized and repaired by the Classical Non-Homologous End-Joining (C-NHEJ) and Homologous Recombination pathways. C-NHEJ includes the core Ku70 and Ku80 (or Ku86) heterodimer that binds DSBs and thus promotes recruitment of accessory downstream NHEJ factors XLF, PAXX, DNA-PKcs, Artemis and other core subunits, XRCC4 and DNA Ligase 4 (Lig4). In the absence of core C-NHEJ factors, DNA repair can be performed by Alternative End-Joining, which likely depends on DNA Ligase 1 and DNA Ligase 3...
September 2017: DNA Repair
https://www.readbyqxmd.com/read/28719838/identification-of-a-prototypical-single-stranded-uracil-dna-glycosylase-from-listeria-innocua
#20
Jing Li, Ye Yang, Jose Guevara, Liangjiang Wang, Weiguo Cao
A recent phylogenetic study on UDG superfamily estimated a new clade of family 3 enzymes (SMUG1-like), which shares a lower homology with canonic SMUG1 enzymes. The enzymatic properties of the newly found putative DNA glycosylase are unknown. To test the potential UDG activity and evaluate phylogenetic classification, we isolated one SMUG1-like glycosylase representative from Listeria innocua (Lin). A biochemical screening of DNA glycosylase activity in vitro indicates that Lin SMUG1-like glycosylase is a single-strand selective uracil DNA glycosylase...
September 2017: DNA Repair
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