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https://www.readbyqxmd.com/read/28551686/human-rad52-interactions-with-replication-protein-a-and-the-rad51-presynaptic-complex
#1
Chu Jian Ma, YoungHo Kwon, Patrick Sung, Eric C Greene
Rad52 is a highly-conserved protein involved in the repair of DNA damage. Human RAD52 has been shown to mediate ssDNA annealing and is synthetic lethal with mutations in other key recombination proteins. Here, we use single-molecule imaging and ssDNA curtains to examine the binding interactions of human RAD52 with RPA-coated ssDNA, and we monitor the fate of RAD52 during assembly of the presynaptic complex. We show that RAD52 binds tightly to the RPA-ssDNA complex and imparts an inhibitory effect on RPA turnover...
May 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28545975/quinazolinone-derivatives-as-inhibitors-of-homologous-recombinase-rad51
#2
Ambber Ward, Lilong Dong, Jonathan M Harris, Kum Kum Khanna, Fares Al-Ejeh, David P Fairlie, Adrian P Wiegmans, Ligong Liu
RAD51 is a vital component of the homologous recombination DNA repair pathway and is overexpressed in drug-resistant cancers, including aggressive triple negative breast cancer (TNBC). A proposed strategy for improving therapeutic outcomes for patients is through small molecule inhibition of RAD51, thereby sensitizing tumor cells to DNA damaging irradiation and/or chemotherapy. Here we report structure-activity relationships for a library of quinazolinone derivatives. A novel RAD51 inhibitor (17) displays up to 15-fold enhanced inhibition of cell growth in a panel of TNBC cell lines compared to compound B02, and approximately 2-fold increased inhibition of irradiation-induced RAD51 foci formation...
May 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28538689/reticulate-evolution-of-the-rock-lizards-meiotic-chromosome-dynamics-and-spermatogenesis-in-diploid-and-triploid-males-of-the-genus-darevskia
#3
Victor Spangenberg, Marine Arakelyan, Eduard Galoyan, Sergey Matveevsky, Ruzanna Petrosyan, Yuri Bogdanov, Felix Danielyan, Oxana Kolomiets
Knowing whether triploid hybrids resulting from natural hybridization of parthenogenetic and bisexual species are fertile is crucial for understanding the mechanisms of reticulate evolution in rock lizards. Here, using males of the bisexual diploid rock lizard species Darevskia raddei nairensis and Darevskia valentini and a triploid hybrid male Darevskia unisexualis × Darevskia valentini, we performed karyotyping and comparative immunocytochemistry of chromosome synapsis and investigated the distribution of RAD51 and MLH1 foci in spread spermatocyte nuclei in meiotic prophase I...
May 24, 2017: Genes
https://www.readbyqxmd.com/read/28536799/stress-induced-transcriptional-changes-and-dna-damage-associated-with-bis-2-ethylhexyl-adipate-exposure-in-zebrafish-danio-rerio-larvae
#4
Halis Boran, Serap Terzi
The present study evaluates potential toxic effects of bis(2-ethylhexyl) adipate (DEHA) plasticizer to larval (72 h post fertilization) zebrafish (Danio rerio) by analyzing changes in expression levels of stress-related genes (p53, rad51 and xrcc5) and assessing possible DNA damage of DEHA in larvae. The lethal concentration for 50% mortality (LC50) in larval zebrafish exposed for 96 h to 0-200 mg L(-1) DEHA was 89.9 ± 8.03 mg L(-1). A concentration-dependent increase in DNA strand breaks was detected in cells from larvae exposed for 96 h to DEHA...
May 24, 2017: Bulletin of Environmental Contamination and Toxicology
https://www.readbyqxmd.com/read/28535142/srs2-promotes-synthesis-dependent-strand-annealing-by-disrupting-dna-polymerase-%C3%AE-extending-d-loops
#5
Jie Liu, Christopher Ede, William D Wright, Steven K Gore, Shirin S Jenkins, Bret D Freudenthal, M Todd Washington, Xavier Veaute, Wolf-Dietrich Heyer
Synthesis-dependent strand annealing (SDSA) is the preferred mode of homologous recombination in somatic cells leading to an obligatory non-crossover outcome, thus avoiding the potential for chromosomal rearrangements and loss of heterozygosity. Genetic analysis identified the Srs2 helicase as a prime candidate to promote SDSA. Here, we demonstrate that Srs2 disrupts D-loops in an ATP-dependent fashion and with a distinct polarity. Specifically, we partly reconstitute the SDSA pathway using Rad51, Rad54, RPA, RFC, DNA Polymerase δ with different forms of PCNA...
May 23, 2017: ELife
https://www.readbyqxmd.com/read/28513990/network-meta-analysis-on-the-effects-of-dna-damage-response-related-gene-mutations-on-overall-survival-of-breast-cancer-based-on-tcga-database
#6
Chang Liu, Hong Chang, Xiao-Han Li, Ya-Fei Qi, Jin-Ou Wang, Ying Zhang, Xiang-Hong Yang
The study was conducted for comparing the effects of 12 DNA damage response gene mutations (CHEK1, CHEK2, RAD51, BRCA1, BRCA2, MLH1, MSH2, ATM, ATR, MDC1, PARP1 and FANCF) on the overall survival (OS) of breast cancer (BC) patients. We searched the Cancer Genome Atlas (TCGA) database from inception to September 2016. Studies that investigated the association between 12 DNA damage responses related genes and BC consolidated into this Network meta-analysis, by comparing directly or indirectly to evaluate the hazard rate (HR) value and the surface under the cumulative sequence ranking curves (SUCRA)...
May 17, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28512217/loss-of-the-homologous-recombination-gene-rad51-leads-to-fanconi-anemia-like-symptoms-in-zebrafish
#7
Jan Gregor Botthof, Ewa Bielczyk-Maczyńska, Lauren Ferreira, Ana Cvejic
RAD51 is an indispensable homologous recombination protein, necessary for strand invasion and crossing over. It has recently been designated as a Fanconi anemia (FA) gene, following the discovery of two patients carrying dominant-negative mutations. FA is a hereditary DNA-repair disorder characterized by various congenital abnormalities, progressive bone marrow failure, and cancer predisposition. In this report, we describe a viable vertebrate model of RAD51 loss. Zebrafish rad51 loss-of-function mutants developed key features of FA, including hypocellular kidney marrow, sensitivity to cross-linking agents, and decreased size...
May 16, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28510199/taxonomic-placement-of-paphiopedilum-rungsuriyanum-cypripedioideae-orchidaceae-based-on-morphological-cytological-and-molecular-analyses
#8
Yung-I Lee, Mei-Chu Chung, Kongmany Sydara, Onevilay Souliya, Sulivong Luang Aphay
BACKGROUND: Paphiopedilum rungsuriyanum from Northern Laos was discovered and described in 2014. It is characterized by having miniature tessellated leaves, a flower having a helmet shaped lip with a V-shaped neckline, and a semi-lunate, 3-dentate staminode with an umbo. These morphological features distinguish P. rungsuriyanum from the other known sections/subgenera of Paphiopedilum, making it difficult to group with existing infrageneric units. RESULTS: Paphiopedilum rungsuriyanum has chromosome number of 2n = 26...
December 2017: Botanical Studies (Taipei, Taiwan)
https://www.readbyqxmd.com/read/28503683/cellular-evaluation-of-diselenonicotinamide-dsna-as-a-radioprotector-against-cell-death-and-dna-damage
#9
M Raghuraman, Prachi Verma, Amit Kunwar, Prasad P Phadnis, V K Jain, K Indira Priyadarsini
Diselenonicotinamide (DSNA), a synthetic organoselenium compound, was evaluated for its radioprotective effect in cellular models. A clonogenic assay in Chinese Hamster Ovary (CHO) cells and an apoptosis assay in murine splenic lymphocytes indicated that pre-treatment with DSNA at a concentration of 25 μM significantly protected them from radiation-induced cell death. Upon irradiation (1-12 Gy), dose-response studies were carried out under similar treatment conditions, and its dose modification factor (DMF) was estimated to be 1...
May 15, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28502582/upregulation-of-rad51-expression-is-associated-with-progression-of-thyroid-carcinoma
#10
R Sarwar, A K Sheikh, I Mahjabeen, K Bashir, S Saeed, M A Kayani
AIMS: RAD51 participates in homologous recombination repair (HRR) of double-stranded DNA breaks (DSBs) which may cause genomic instability and cancer. The aim of this study was to investigate RAD51 gene expression at transcriptional and translational levels to measure mRNA and protein level and to correlate its relationship with proliferation marker, Ki67 in thyroid cancer patients. This study also explored correlation of these genes with different clinicopathological parameters of the study cohort by Spearman's rank correlation coefficient...
May 11, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28501701/radb-acts-in-homologous-recombination-in-the-archaeon-haloferax-volcanii-consistent-with-a-role-as-recombination-mediator
#11
Kayleigh Wardell, Sam Haldenby, Nathan Jones, Susan Liddell, Greg H P Ngo, Thorsten Allers
Homologous recombination plays a central role in the repair of double-strand DNA breaks, the restart of stalled replication forks and the generation of genetic diversity. Regulation of recombination is essential since defects can lead to genome instability and chromosomal rearrangements. Strand exchange is a key step of recombination - it is catalysed by RecA in bacteria, Rad51/Dmc1 in eukaryotes and RadA in archaea. RadB, a paralogue of RadA, is present in many archaeal species. RadB has previously been proposed to function as a recombination mediator, assisting in RadA-mediated strand exchange...
April 26, 2017: DNA Repair
https://www.readbyqxmd.com/read/28492345/the-focinator-v2-0-graphical-interface-four-channels-colocalization-analysis-and-cell-phase-identification
#12
Sebastian Oeck, Nathalie M Malewicz, Sebastian Hurst, Klaudia Al-Refae, Adam Krysztofiak, Verena Jendrossek
The quantitative analysis of foci plays an important role in various cell biological methods. In the fields of radiation biology and experimental oncology, the effect of ionizing radiation, chemotherapy or molecularly targeted drugs on DNA damage induction and repair is frequently performed by the analysis of protein clusters or phosphorylated proteins recruited to so called repair foci at DNA damage sites, involving for example γ-H2A.X, 53BP1 or RAD51. We recently developed "The Focinator" as a reliable and fast tool for automated quantitative and qualitative analysis of nuclei and DNA damage foci...
May 11, 2017: Radiation Research
https://www.readbyqxmd.com/read/28487407/acute-inactivation-of-the-replicative-helicase-in-human-cells-triggers-mcm8-9-dependent-dna-synthesis
#13
Toyoaki Natsume, Kohei Nishimura, Sheroy Minocherhomji, Rahul Bhowmick, Ian D Hickson, Masato T Kanemaki
DNA replication fork progression can be disrupted at difficult to replicate loci in the human genome, which has the potential to challenge chromosome integrity. This replication fork disruption can lead to the dissociation of the replisome and the formation of DNA damage. To model the events stemming from replisome dissociation during DNA replication perturbation, we used a degron-based system for inducible proteolysis of a subunit of the replicative helicase. We show that MCM2-depleted cells activate a DNA damage response pathway and generate replication-associated DNA double-strand breaks (DSBs)...
May 9, 2017: Genes & Development
https://www.readbyqxmd.com/read/28477336/rad51-as-a-potential-surrogate-marker-for-dna-repair-capacity-in-solid-malignancies
#14
REVIEW
Mariam Gachechiladze, Josef Škarda, Alex Soltermann, Markus Joerger
Targeting deficient mechanisms of cellular DNA repair still represents the basis for the treatment of the majority of solid tumors, and increased DNA repair capacity is a hallmark mechanism of resistance not only to DNA-damaging treatments such as cytotoxic drugs and radiotherapy, but also to small molecule targeted drugs such as inhibitors of poly-ADP ribose polymerase (PARP). Hence, there is substantial medical need for potent and convenient biomarkers of individual response to DNA-targeted treatment in personalized cancer care...
May 6, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28476890/sequence-imperfections-and-base-triplet-recognition-by-the-rad51-reca-family-of-recombinases
#15
Ja Yil Lee, Justin B Steinfeld, Zhi Qi, YoungHo Kwon, Patrick Sung, Eric C Greene
Homologous recombination plays key roles in double strand break repair, rescue and repair of stalled replication forks, and meiosis. The broadly conserved Rad51/RecA family of recombinases catalyze the DNA strand invasion reaction that takes place during homologous recombination. We have established ssDNA curtain assays for measuring individual base triplet steps during the early stages of strand invasion. Here we examine how base triplet stepping by RecA, Rad51, and Dmc1 is affected by DNA sequence imperfections, such as single and multiple mismatches, abasic sites, and single nucleotide insertions...
May 5, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28475874/unprotected-replication-forks-are-converted-into-mitotic-sister-chromatid-bridges
#16
Anissia Ait Saada, Ana Teixeira-Silva, Ismail Iraqui, Audrey Costes, Julien Hardy, Giulia Paoletti, Karine Fréon, Sarah A E Lambert
Replication stress and mitotic abnormalities are key features of cancer cells. Temporarily paused forks are stabilized by the intra-S phase checkpoint and protected by the association of Rad51, which prevents Mre11-dependent resection. However, if a fork becomes dysfunctional and cannot resume, this terminally arrested fork is rescued by a converging fork to avoid unreplicated parental DNA during mitosis. Alternatively, dysfunctional forks are restarted by homologous recombination. Using fission yeast, we report that Rad52 and the DNA binding activity of Rad51, but not its strand-exchange activity, act to protect terminally arrested forks from unrestrained Exo1-nucleolytic activity...
May 4, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28471392/taking-a-bad-turn-compromised-dna-damage-response-in-leukemia
#17
REVIEW
Nadine Nilles, Birthe Fahrenkrog
Genomic integrity is of outmost importance for the survival at the cellular and the organismal level and key to human health. To ensure the integrity of their DNA, cells have evolved maintenance programs collectively known as the DNA damage response. Particularly challenging for genome integrity are DNA double-strand breaks (DSB) and defects in their repair are often associated with human disease, including leukemia. Defective DSB repair may not only be disease-causing, but further contribute to poor treatment outcome and poor prognosis in leukemia...
May 4, 2017: Cells
https://www.readbyqxmd.com/read/28466382/assessment-of-htlv-1-proviral-load-lat-bim-c-fos-and-rad51-gene-expression-in-adult-t-cell-leukemia-lymphoma
#18
Samaneh Ramezani, Abbas Shirdel, Houshang Rafatpanah, Mohammad Mehdi Akbarin, Hanieh Tarokhian, Hossein Rahimi, Alireza Bari, Hamid Reza Jahantigh, Seyed Abdolrahim Rezaee
Adult T cell leukemia/lymphoma (ATLL) is a life-threatening malignancy of HTLV-1 infected Th lymphocytes. In the present study host-virus interactions were investigated by assessment of HTLV-1 proviral load (PVL) and host gene expression. A cross-sectional study was carried out on 18 ATLL, 10 HAM/TSP patients and 18 HTLV-1 asymptomatic carriers (ACs). DNA and mRNA of the peripheral blood mononuclear cells were extracted for PVL and LAT, BIM, c-FOS and RAD51 gene expression measurement using qRT-PCR. The mean PVL in ATLL patients was 11,430 ± 3770 copies/10(4) which was statistically higher than ACs, 530 ± 119 copies/10(4), (p < 0...
May 2, 2017: Medical Microbiology and Immunology
https://www.readbyqxmd.com/read/28461573/genetic-and-small-molecule-disruption-of-the-aid-rad51-axis-similarly-protects-nonobese-diabetic-mice-from-type-1-diabetes-through-expansion-of-regulatory-b-lymphocytes
#19
Jeremy J Ratiu, Jeremy J Racine, Muneer G Hasham, Qiming Wang, Jane A Branca, Harold D Chapman, Jing Zhu, Nina Donghia, Vivek Philip, William H Schott, Clive Wasserfall, Mark A Atkinson, Kevin D Mills, Caroline M Leeth, David V Serreze
B lymphocytes play a key role in type 1 diabetes (T1D) development by serving as a subset of APCs preferentially supporting the expansion of autoreactive pathogenic T cells. As a result of their pathogenic importance, B lymphocyte-targeted therapies have received considerable interest as potential T1D interventions. Unfortunately, the B lymphocyte-directed T1D interventions tested to date failed to halt β cell demise. IgG autoantibodies marking humans at future risk for T1D indicate that B lymphocytes producing them have undergone the affinity-maturation processes of class switch recombination and, possibly, somatic hypermutation...
May 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28453695/genetic-variants-of-dna-repair-related-genes-predict-efficacy-of-tas-102-in-patients-with-refractory-metastatic-colorectal-cancer
#20
M Suenaga, M Schirripa, S Cao, W Zhang, D Yang, S Murgioni, D Rossini, F Marmorino, A Mennitto, Y Ning, S Okazaki, M D Berger, Y Miyamoto, R Gopez, A Barzi, T Yamaguchi, F Loupakis, H-J Lenz
Background: Tri-phosphorylated trifluridine (FTD) incorporation into DNA is TAS-102's main anti-tumor action. We tested whether genetic polymorphisms in homologous recombination (HR) and cell cycle checkpoint pathway for DNA repair is associated with outcomes in refractory metastatic colorectal cancer (mCRC) patients treated with TAS-102. Patients and methods: We analyzed genomic DNA extracted from 233 samples of three cohorts: an evaluation cohort of 52 patients receiving TAS-102, a validation cohort of 129 patients receiving TAS-102 and a control cohort of 52 patients receiving regorafenib...
May 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
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