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https://www.readbyqxmd.com/read/27926907/mammalian-meiotic-recombination-a-toolbox-for-genome-evolution
#1
Laia Capilla, Montserrat Garcia Caldés, Aurora Ruiz-Herrera
Meiotic recombination is a process that increases genetic diversity and is fundamental for sexual reproduction. Determining by which mechanisms genetic variation is generated and maintained across different phylogenetic groups provides the basis for our understanding of biodiversity and evolution. In this review, we go through different aspects of this essential phenomenon, paying special attention to mammals. We provide a comprehensive view on the organization of meiotic chromosomes and the mechanisms involved in the formation and genomic distribution of recombination hotspots, focusing on the factors influencing the formation and repair of the massive amount of self-induced DNA breaks in early stages of meiosis...
December 8, 2016: Cytogenetic and Genome Research
https://www.readbyqxmd.com/read/27925687/dna-base-excision-repair-proteins-ape-1-and-xrcc-1-are-overexpressed-in-oral-tongue-squamous-cell-carcinoma
#2
Thalita Santana, Melka Coêlho Sá, Edilmar de Moura Santos, Hébel Cavalcanti Galvão, Ricardo D Coletta, Roseana de Almeida Freitas
BACKGROUND: DNA repair systems play a critical role in protecting the human genome from damage caused by carcinogens. Modifications in DNA repair genes may be responsible for tumor development and resistance of malignant cells to chemotherapeutic agents. The major pathway for oxidative DNA damage repair is the base excision repair pathway. This study aimed to assess the immunoexpression of DNA repair proteins APE-1 and XRCC-1 and its association with clinical, histological and survival parameters in oral tongue squamous cell carcinoma in order to investigate a possible role for those proteins in tumor behavior...
December 7, 2016: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/27925473/the-role-of-cancer-stem-cells-in-tumor-heterogeneity-and-resistance-to-therapy
#3
Christina Valbirk Konrad, Reshma Murali, Binitha Anu Varghese, Radhika Nair
Cancer is a heterogenous disease displaying marked inter- and intra-tumoral diversity. The existence of cancer stem cells (CSCs) has been experimentally demonstrated in a number of cancer types as a subpopulation of tumor cells that drives the tumorigenic and metastatic properties of the entire cancer. Thus, eradication of the CSC population is critical for the complete ablation of a tumor. This is, however, confounded by the inherent resistance of CSCs to standard anticancer therapies, eventually leading to the outgrowth of resistant tumor cells and relapse in patients...
September 3, 2016: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/27925276/conformational-and-intermolecular-interaction-dynamics-of-photolyase-cryptochrome-proteins-monitored-by-the-time-resolved-diffusion-technique
#4
Masato Kondoh, Masahide Terazima
Cryptochrome (CRY), a blue light sensor protein, possesses a similar domain structure to photolyase (PHR) that, upon absorption of light, repairs DNA damage. In this review, we compare the reaction dynamics of these systems by monitoring the reaction kinetics of conformation change and intermolecular interaction change based on time-dependent diffusion coefficient measurements obtained by using the pulsed laser-induced transient grating technique. Using this method, time-dependent biomolecular interactions, such as transient dissociation reactions in solution, have been successfully detected in real time...
December 7, 2016: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/27925218/insights-into-light-driven-dna-repair-by-photolyases-challenges-and-opportunities-for-electronic-structure-theory
#5
Shirin Faraji, Andreas Dreuw
UV radiation causes two of the most abundant mutagenic and cytotoxic DNA lesions: cyclobutane pyrimidine dimers and 6-4 photoproducts. (6-4) photolyases are light-activated enzymes that selectively bind to DNA and trigger repair of mutagenic 6-4 photoproducts via photoinduced electron transfer from flavin adenine dinucleotide anion (FADH(-) ) to the lesion triggering repair. This review provides an overview of the sequential steps of the repair process, i.e. light absorption and resonance energy transfer, photo-induced electron transfer, and electron-induced splitting mechanisms, with an emphasis on the role of theory and computation...
December 7, 2016: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/27925203/the-genetic-landscape-of-breast-carcinomas-with-neuroendocrine-differentiation
#6
Caterina Marchiò, Felipe C Geyer, Charlotte Ky Ng, Salvatore Piscuoglio, Maria R De Filippo, Marco Cupo, Anne M Schultheis, Raymond S Lim, Kathleen A Burke, Elena Guerini-Rocco, Mauro Papotti, Larry Norton, Anna Sapino, Britta Weigelt, Jorge S Reis-Filho
Neuroendocrine breast carcinomas (NBCs) account for 2-5% of all invasive breast cancers and are histologically similar to neuroendocrine tumours from other sites. They typically express oestrogen receptor (ER), are HER2-negative and of luminal subtype. Here we sought to define the mutational profile of NBCs, and to investigate whether NBCs and common forms of luminal (ER+/HER2-) breast cancer display distinct repertoires of somatic mutations. Eighteen ER+/HER2- NBCs, defined as harbouring >50% of tumour cells expressing chromogranin A and/or synaptophysin, and matched normal tissue were microdissected and subjected to massively parallel sequencing targeting all exons of 254 genes most frequently mutated in breast cancer and/or related to DNA repair...
December 7, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/27924561/detection-and-functional-analysis-of-sumo-modified-mek
#7
Yuji Kubota, Mutsuhiro Takekawa
Small ubiquitin-like modifier (SUMO) is a posttranslational protein modifier that binds target proteins covalently (protein sumoylation) and remarkably alters their functions. Protein sumoylation has been linked to various cellular functions such as cell division, DNA repair, and import of nuclear proteins. Thus, its dysregulation is implicated in diverse human diseases such as neurodegenerative disorders and cancers. We recently found that the kinase activity of MEK proteins, which function as central components of the ERK-MAPK cascade and amplify an extracellular proliferation signal, is negatively regulated by sumoylation...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924191/a-decade-of-biochemical-and-structural-studies-of-the-dna-repair-machinery-of-deinococcus-radiodurans-major-findings-functional-and-mechanistic-insight-and-challenges
#8
REVIEW
Joanna Timmins, Elin Moe
No abstract text is available yet for this article.
2016: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/27924075/histone-variants-on-the-move-substrates-for-chromatin-dynamics
#9
Paul B Talbert, Steven Henikoff
Most histones are assembled into nucleosomes behind the replication fork to package newly synthesized DNA. By contrast, histone variants, which are encoded by separate genes, are typically incorporated throughout the cell cycle. Histone variants can profoundly change chromatin properties, which in turn affect DNA replication and repair, transcription, and chromosome packaging and segregation. Recent advances in the study of histone replacement have elucidated the dynamic processes by which particular histone variants become substrates of histone chaperones, ATP-dependent chromatin remodellers and histone-modifying enzymes...
December 7, 2016: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/27924031/ubiquitylation-dependent-regulation-of-neil1-by-mule-and-trim26-is-required-for-the-cellular-dna-damage-response
#10
Matthew J Edmonds, Rachel J Carter, Catherine M Nickson, Sarah C Williams, Jason L Parsons
Endonuclease VIII-like protein 1 (NEIL1) is a DNA glycosylase involved in initiating the base excision repair pathway, the major cellular mechanism for repairing DNA base damage. Here, we have purified the major E3 ubiquitin ligases from human cells responsible for regulation of NEIL1 by ubiquitylation. Interestingly, we have identified two enzymes that catalyse NEIL1 polyubiquitylation, Mcl-1 ubiquitin ligase E3 (Mule) and tripartite motif 26 (TRIM26). We demonstrate that these enzymes are capable of polyubiquitylating NEIL1 in vitro, and that both catalyse ubiquitylation of NEIL1 within the same C-terminal lysine residues...
October 18, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27924011/roles-for-aprin-pds5b-in-homologous-recombination-and-in-ovarian-cancer-prediction
#11
Anthony M Couturier, Hubert Fleury, Anne-Marie Patenaude, Victoria L Bentley, Amélie Rodrigue, Yan Coulombe, Joshi Niraj, Joris Pauty, Jason N Berman, Graham Dellaire, Javier M Di Noia, Anne-Marie Mes-Masson, Jean-Yves Masson
APRIN (PDS5 cohesin associated factor B) interacts with both the cohesin complex and the BRCA2 tumor suppressor. How APRIN influences cohesion and DNA repair processes is not well understood. Here, we show that APRIN is recruited to DNA damage sites. We find that APRIN interacts directly with RAD51, PALB2 and BRCA2. APRIN stimulates RAD51-mediated DNA strand invasion. APRIN also binds DNA with an affinity for D-loop structures and single-strand (ss) DNA. APRIN is a new homologous recombination (HR) mediator as it counteracts the RPA inhibitory effect on RAD51 loading to ssDNA...
October 24, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27924007/bridging-of-double-stranded-breaks-by-the-nonhomologous-end-joining-ligation-complex-is-modulated-by-dna-end-chemistry
#12
Dylan A Reid, Michael P Conlin, Yandong Yin, Howard H Chang, Go Watanabe, Michael R Lieber, Dale A Ramsden, Eli Rothenberg
The nonhomologous end-joining (NHEJ) pathway is the primary repair pathway for DNA double strand breaks (DSBs) in humans. Repair is mediated by a core complex of NHEJ factors that includes a ligase (DNA Ligase IV; L4) that relies on juxtaposition of 3' hydroxyl and 5' phosphate termini of the strand breaks for catalysis. However, chromosome breaks arising from biological sources often have different end chemistries, and how these different end chemistries impact the way in which the core complex directs the necessary transitions from end pairing to ligation is not known...
December 6, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27924006/the-homologous-recombination-protein-rad51d-protects-the-genome-from-large-deletions
#13
Wade A Reh, Rodney S Nairn, Megan P Lowery, Karen M Vasquez
Homologous recombination (HR) is a DNA double-strand break (DSB) repair pathway that protects the genome from chromosomal instability. RAD51 mediator proteins (i.e. paralogs) are critical for efficient HR in mammalian cells. However, how HR-deficient cells process DSBs is not clear. Here, we utilized a loss-of-function HR-reporter substrate to simultaneously monitor HR-mediated gene conversion and non-conservative mutation events. The assay is designed around a heteroallelic duplication of the Aprt gene at its endogenous locus in isogenic Chinese hamster ovary cell lines...
December 6, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27924002/sfpq%C3%A2-nono-and-xlf-function-separately-and-together-to-promote-dna-double-strand-break-repair-via-canonical-nonhomologous-end-joining
#14
Lahcen Jaafar, Zhentian Li, Shuyi Li, William S Dynan
A complex of two related mammalian proteins, SFPQ and NONO, promotes DNA double-strand break repair via the canonical nonhomologous end joining (c-NHEJ) pathway. However, its mechanism of action is not fully understood. Here we describe an improved SFPQ•NONO-dependent in vitro end joining assay. We use this system to demonstrate that the SFPQ•NONO complex substitutes in vitro for the core c-NHEJ factor, XLF. Results are consistent with a model where SFPQ•NONO promotes sequence-independent pairing of DNA substrates, albeit in a way that differs in detail from XLF...
December 6, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27924001/histone-chaperone-activity-of-arabidopsis-thaliana-nrp1-is-blocked-by-cytochrome-c
#15
Katiuska González-Arzola, Antonio Díaz-Quintana, Francisco Rivero-Rodríguez, Adrián Velázquez-Campoy, Miguel A De la Rosa, Irene Díaz-Moreno
Higher-order plants and mammals use similar mechanisms to repair and tolerate oxidative DNA damage. Most studies on the DNA repair process have focused on yeast and mammals, in which histone chaperone-mediated nucleosome disassembly/reassembly is essential for DNA to be accessible to repair machinery. However, little is known about the specific role and modulation of histone chaperones in the context of DNA damage in plants. Here, the histone chaperone NRP1, which is closely related to human SET/TAF-Iβ, was found to exhibit nucleosome assembly activity in vitro and to accumulate in the chromatin of Arabidopsis thaliana after DNA breaks...
December 6, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27923995/homologous-recombination-in-budding-yeast-expressing-the-human-rad52-gene-reveals-a-rad51-independent-mechanism-of-conservative-double-strand-break-repair
#16
Glenn M Manthey, Alissa D Clear, Lauren C Liddell, Maria C Negritto, Adam M Bailis
RAD52 is a homologous recombination (HR) protein that is conserved from bacteriophage to humans. Simultaneously attenuating expression of both the RAD52 gene, and the HR and tumor suppressor gene, BRCA2, in human cells synergistically reduces HR - indicating that RAD52 and BRCA2 control independent mechanisms of HR. We have expressed the human RAD52 gene (HsRAD52) in budding yeast strains lacking the endogenous RAD52 gene and found that HsRAD52 supports repair of DNA double-strand breaks (DSB) by a mechanism of HR that conserves genome structure...
December 6, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27923991/a-specific-dna-nanoprobe-for-tracking-the-activities-of-human-apurinic-apyrimidinic-endonuclease-1-in-living-cells
#17
Junqiu Zhai, Yibin Liu, Shan Huang, Simin Fang, Meiping Zhao
Human apurinic/apyrimidinic endonuclease/redox effector factor 1 (APE1) is an essential DNA repair protein. Herein, we demonstrate that avidin-oriented abasic site-containing DNA strands (AP-DNA) on the surface of silica coated magnetic nanoparticles (SiMNP) can selectively respond to APE1 while resist the digestion by other nucleases. Mechanism studies have revealed that avidin may serve as an organizer protein and recruit APE1 to the DNA substrates on the nanoparticles via strong and specific interactions...
December 6, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27923837/the-nci-60-methylome-and-its-integration-into-cellminer
#18
William C Reinhold, Sudhir Varma, Margot Sunshine, Vinodh Rajapakse, Augustin Luna, Kurt W Kohn, Holly Stevenson, Yonghong Wang, Holger Heyn, Vanesa Nogales, Sebastian Moran, David J Goldstein, James H Doroshow, Paul S Meltzer, Manel Esteller, Yves Pommier
A unique resource for systems pharmacology and genomic studies is the NCI-60 cancer cell line panel, which provides data for the largest publicly available library of compounds with cytotoxic activity (~21,000 compounds), including 108 FDA-approved and 70 clinical trial drugs as well as genomic data, including whole-exome sequencing, gene and microRNA transcripts, DNA copy number, and protein levels. Here we provide the first readily usable genome-wide DNA methylation database for the NCI-60, including 485,577 probes from the Infinium HumanMethylation450k BeadChip array, which yielded DNA methylation signatures for 17,559 genes integrated into our open access CellMiner version 2...
December 6, 2016: Cancer Research
https://www.readbyqxmd.com/read/27923713/when-transcription-goes-on-holliday-double-holliday-junctions-block-rna-polymerase-ii-transcription-in-vitro
#19
Anne Pipathsouk, Boris P Belotserkovskii, Philip C Hanawalt
Non-canonical DNA structures can obstruct transcription. This transcription blockage could have various biological consequences, including genomic instability and gratuitous transcription-coupled repair. Among potential structures causing transcription blockage are Holliday junctions (HJ), which can be generated as intermediates in homologous recombination or during processing of stalled replication forks. Of particular interest is the double Holliday junction (DHJ), which contains two HJs. Topological considerations impose the constraint that the total number of helical turns in the DNA duplexes between the junctions cannot be altered as long as the flanking DNA duplexes are intact...
December 3, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27923681/evaluation-of-dna-damaging-potential-of-bisphenol-a-and-its-selected-analogs-in-human-peripheral-blood-mononuclear-cells-in-vitro-study
#20
Katarzyna Mokra, Agnieszka Kuźmińska-Surowaniec, Katarzyna Woźniak, Jaromir Michałowicz
In the present study, we have investigated DNA-damaging potential of BPA and its analogs, i.e. bisphenol S (BPS), bisphenol F (BPF) and bisphenol AF (BPAF) in human peripheral blood mononuclear cells (PBMCs) using the alkaline and neutral versions of the comet assay, which allowed to evaluate DNA single strand-breaks (SSBs) and double strandbreaks (DSBs). The use of the alkaline version of comet assay made also possible to analyze the kinetics of DNA repair in PBMCs after exposure of the cells to BPA or its analogs...
December 3, 2016: Food and Chemical Toxicology
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