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https://www.readbyqxmd.com/read/28749109/xpg-asp1104his-xrcc2-rs3218536-a-g-and-rad51-135g-c-gene-polymorphisms-and-colorectal-cancer-risk-a-meta-analysis
#1
Ebrahim Eskandari, Alireza Rezaifar, Mohammad Hashemi
Background: DNA repair mechanisms are crucial for sustaining DNA integrity and preventing carcinogenesis. The xeroderma pigmentosum group G (XPG), X-ray repair cross complementing group 2 (XRCC2) and RAD51 are candidate genes for DNA repair pathways. Methods: We performed a meta-analysis of 26 studies that assessed the impact of XPG Asp1104His, XRCC2 rs3218536 A/G and RAD51 135G/C polymorphisms on colorectal cancer (CRC) risk. This study included 10288 CRC patients and 11885 controls, and odds ratio (OR) with its 95% confidence interval (CI) were used to calculate the strength of association...
July 27, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28747557/%C3%AE-h2ax-53bp1-and-rad51-protein-foci-changes-in-mesenchymal-stem-cells-during-prolonged-x-ray-irradiation
#2
Anastasia Tsvetkova, Ivan V Ozerov, Margarita Pustovalova, Anna Grekhova, Petr Eremin, Natalia Vorobyeva, Ilya Eremin, Andrey Pulin, Vadim Zorin, Pavel Kopnin, Sergey Leonov, Alex Zhavoronkov, Dmitry Klokov, Andreyan N Osipov
At high exposure levels ionizing radiation is a carcinogen. Little is known about how human stem cells, which are known to contribute to tumorigenesis, respond to prolonged radiation exposures. We studied formation of DNA double strand breaks, accessed as γH2AX and 53BP1 foci, in human mesenchymal stem cells (MSCs) exposed to either acute (5400 mGy/h) or prolonged (270 mGy/h) X-irradiation. We show a linear γH2AX and 53BP1 dose response for acute exposures. In contrast, prolonged exposure resulted in a dose-response curve that had an initial linear portion followed by a plateau...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28747513/repression-of-bet-activity-sensitizes-homologous-recombination-proficient-cancers-to-parp-inhibition
#3
Lu Yang, Youyou Zhang, Weiwei Shan, Zhongyi Hu, Jiao Yuan, Jingjiang Pi, Yueying Wang, Lingling Fan, Zhaoqing Tang, Chunsheng Li, Xiaowen Hu, Janos L Tanyi, Yi Fan, Qihong Huang, Kathleen Montone, Chi V Dang, Lin Zhang
Strategies to enhance response to poly(adenosine diphosphate-ribose) polymerase inhibitor (PARPi) in primary and acquired homologous recombination (HR)-proficient tumors would be a major advance in cancer care. We used a drug synergy screen that combined a PARPi, olaparib, with 20 well-characterized epigenetic drugs and identified bromodomain and extraterminal domain inhibitors (BETis; JQ1, I-BET762, and OTX015) as drugs that acted synergistically with olaparib in HR-proficient cancer cells. Functional assays demonstrated that repressed BET activity reduces HR and thus enhances PARPi-induced DNA damage in cancer cells...
July 26, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28745000/sycp3-regulates-strand-invasion-activities-of-rad51-and-dmc1
#4
Wataru Kobayashi, Noriko Hosoya, Shinichi Machida, Kiyoshi Miyagawa, Hitoshi Kurumizaka
The synaptonemal complex is a higher-ordered proteinaceous architecture formed between homologous chromosomes. SYCP3 is a major component of the lateral/axial elements in the synaptonemal complex and is essential for meiotic recombination. Previous genetic studies showed that SYCP3 functions in meiotic homologous recombination biased to interhomologous chromosomes, by regulating the strand invasion activities of the RAD51 and DMC1 recombinases. However, the mechanism by which SYCP3 regulates RAD51- and DMC1-mediated strand invasion remains elusive...
July 26, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28743957/ubiquitin-specific-protease-21-stabilizes-brca2-to-control-dna-repair-and-tumor-growth
#5
Jinping Liu, Alex Kruswick, Hien Dang, Andy D Tran, So Mee Kwon, Xin Wei Wang, Philipp Oberdoerffer
Tumor growth relies on efficient DNA repair to mitigate the detrimental impact of DNA damage associated with excessive cell division. Modulating repair factor function, thus, provides a promising strategy to manipulate malignant growth. Here, we identify the ubiquitin-specific protease USP21 as a positive regulator of BRCA2, a key mediator of DNA repair by homologous recombination. USP21 interacts with, deubiquitinates and stabilizes BRCA2 to promote efficient RAD51 loading at DNA double-strand breaks. As a result, depletion of USP21 decreases homologous recombination efficiency, causes an increase in DNA damage load and impairs tumor cell survival...
July 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28735897/radx-promotes-genome-stability-and-modulates-chemosensitivity-by-regulating-rad51-at-replication-forks
#6
Huzefa Dungrawala, Kamakoti P Bhat, Rémy Le Meur, Walter J Chazin, Xia Ding, Shyam K Sharan, Sarah R Wessel, Aditya A Sathe, Runxiang Zhao, David Cortez
RAD51 promotes homology-directed repair (HDR), replication fork reversal, and stalled fork protection. Defects in these functions cause genomic instability and tumorigenesis but also generate hypersensitivity to cancer therapeutics. Here we describe the identification of RADX as an RPA-like, single-strand DNA binding protein. RADX is recruited to replication forks, where it prevents fork collapse by regulating RAD51. When RADX is inactivated, excessive RAD51 activity slows replication elongation and causes double-strand breaks...
July 19, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28729862/rad51-interacts-with-non-structural-3-protein-of-hepatitis-c-virus-and-regulates-viral-production
#7
Kidong Son, Tram T T Nguyen, Jae-Woong Choi, Long V Pham, Trang T D Luong, Yun-Sook Lim, Soon B Hwang
Hepatitis C virus (HCV) is a leading cause of chronic liver disease affecting over 170 million people worldwide. Chronic infection with HCV progresses to liver fibrosis, cirrhosis, and hepatocellular carcinoma. HCV exploits host cellular factors for viral propagation. To investigate the cellular factors required for HCV propagation, we screened a siRNA library targeting human cell cycle genes using cell culture grown HCV-infected cells. In the present study, we selected and characterized a gene encoding Rad51...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28729482/brca1-and-brca2-tumor-suppressors-protect-against-endogenous-acetaldehyde-toxicity
#8
Eliana Mc Tacconi, Xianning Lai, Cecilia Folio, Manuela Porru, Gijs Zonderland, Sophie Badie, Johanna Michl, Irene Sechi, Mélanie Rogier, Verónica Matía García, Ankita Sati Batra, Oscar M Rueda, Peter Bouwman, Jos Jonkers, Anderson Ryan, Bernardo Reina-San-Martin, Joannie Hui, Nelson Tang, Alejandra Bruna, Annamaria Biroccio, Madalena Tarsounas
Maintenance of genome integrity requires the functional interplay between Fanconi anemia (FA) and homologous recombination (HR) repair pathways. Endogenous acetaldehyde, a product of cellular metabolism, is a potent source of DNA damage, particularly toxic to cells and mice lacking the FA protein FANCD2. Here, we investigate whether HR-compromised cells are sensitive to acetaldehyde, similarly to FANCD2-deficient cells. We demonstrate that inactivation of HR factors BRCA1, BRCA2, or RAD51 hypersensitizes cells to acetaldehyde treatment, in spite of the FA pathway being functional...
July 20, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28723680/meiotic-recombination-in-the-giraffe-g-reticulata
#9
Miluse Vozdova, Jan Fröhlich, Svatava Kubickova, Hana Sebestova, Jiri Rubes
Recently, the reticulated giraffe (G. reticulata) was identified as a distinct species, which emphasized the need for intensive research in this interesting animal. To shed light on the meiotic process as a source of biodiversity, we analysed the frequency and distribution of meiotic recombination in 2 reticulated giraffe males. We used immunofluorescence detection of synaptonemal complex protein (SYCP3), meiotic double strand breaks (DSB, marked as RAD51 foci) in leptonema, and crossovers (COs, as MLH1 foci) in pachynema...
July 20, 2017: Cytogenetic and Genome Research
https://www.readbyqxmd.com/read/28698370/g9a-coordinates-with-the-rpa-complex-to-promote-dna-damage-repair-and-cell-survival
#10
Qiaoyan Yang, Qian Zhu, Xiaopeng Lu, Yipeng Du, Linlin Cao, Changchun Shen, Tianyun Hou, Meiting Li, Zhiming Li, Chaohua Liu, Di Wu, Xingzhi Xu, Lina Wang, Haiying Wang, Ying Zhao, Yang Yang, Wei-Guo Zhu
Histone methyltransferase G9a has critical roles in promoting cancer-cell growth and gene suppression, but whether it is also associated with the DNA damage response is rarely studied. Here, we report that loss of G9a impairs DNA damage repair and enhances the sensitivity of cancer cells to radiation and chemotherapeutics. In response to DNA double-strand breaks (DSBs), G9a is phosphorylated at serine 211 by casein kinase 2 (CK2) and recruited to chromatin. The chromatin-enriched G9a can then directly interact with replication protein A (RPA) and promote loading of the RPA and Rad51 recombinase to DSBs...
July 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28694245/fundamental-cell-cycle-kinases-collaborate-to-ensure-timely-destruction-of-the-synaptonemal-complex-during-meiosis
#11
Bilge Argunhan, Wing-Kit Leung, Negar Afshar, Yaroslav Terentyev, Vijayalakshmi V Subramanian, Yasuto Murayama, Andreas Hochwagen, Hiroshi Iwasaki, Tomomi Tsubouchi, Hideo Tsubouchi
The synaptonemal complex (SC) is a proteinaceous macromolecular assembly that forms during meiotic prophase I and mediates adhesion of paired homologous chromosomes along their entire lengths. Although prompt disassembly of the SC during exit from prophase I is a landmark event of meiosis, the underlying mechanism regulating SC destruction has remained elusive. Here, we show that DDK (Dbf4-dependent Cdc7 kinase) is central to SC destruction. Upon exit from prophase I, Dbf4, the regulatory subunit of DDK, directly associates with and is phosphorylated by the Polo-like kinase Cdc5...
July 10, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28681469/differential-expression-of-homologous-recombination-dna-repair-genes-in-the-early-and-advanced-stages-of-myelodysplastic-syndrome
#12
Jan Valka, Jitka Vesela, Hana Votavova, Michaela Dostalova-Merkerova, Zuzana Horakova, Vit Campr, Jana Brezinova, Zuzana Zemanova, Anna Jonasova, Jaroslav Cermak, Monika Belickova
BACKGROUND: The high incidence of mutations and cytogenetic abnormalities in patients with myelodysplastic syndrome (MDS) suggests that defects in DNA repair mechanisms. We monitored DNA repair pathways in MDS and their alterations during disease progression. METHODS: Expression profiling of DNA repair genes was performed on CD34+ cells and paired samples were used for monitoring of RAD51 and XRCC2 gene expression during disease progression. Immunohistochemical staining for RAD51 was done on histology samples...
July 5, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28667302/e2f1-regulated-long-non-coding-rna-rad51-as1-promotes-cell-cycle-progression-inhibits-apoptosis-and-predicts-poor-prognosis-in-epithelial-ovarian-cancer
#13
Xiaodan Zhang, Guoping Liu, Junjun Qiu, Ning Zhang, Jingxin Ding, Keqin Hua
Long non-coding RNA RAD51 antisense RNA 1 (RAD51-AS1, also known as TODRA) has been shown to be down-regulated by E2F1, a key cell cycle and apoptosis regulator, in breast cancer. Little is known regarding the role of RAD51-AS1 in disease. Here, we investigate the role of RAD51-AS1 in epithelial ovarian cancer (EOC). Using luciferase reporter and chromatin immunoprecipitation experiments, we verified RAD51-AS1 as a target of E2F1 under negative regulation in EOC. We then examined RAD51-AS1 expression in EOC samples using in situ hybridization (ISH)...
June 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28667173/a-time-for-promiscuity-in-a-eukaryotic-recombinase
#14
REVIEW
Maria Spies
The exchange of DNA strands between broken and intact molecules lies at the heart of fundamental cellular processes ranging from repairing DNA damage by homologous recombination to generation of genetic diversity during sexual reproduction. New work by Lee and colleagues utilizes the DNA curtain method, an elegant single-molecule technique, to demonstrate common and idiosyncratic features in the DNA strand exchange mechanisms of three RecA-family recombinases, bacterial RecA, and eukaryotic Rad51 and Dmc1 proteins...
June 30, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28666126/telomere-length-determines-terra-and-r-loop-regulation-through-the-cell-cycle
#15
Marco Graf, Diego Bonetti, Arianna Lockhart, Kamar Serhal, Vanessa Kellner, André Maicher, Pascale Jolivet, Maria Teresa Teixeira, Brian Luke
Maintenance of a minimal telomere length is essential to prevent cellular senescence. When critically short telomeres arise in the absence of telomerase, they can be repaired by homology-directed repair (HDR) to prevent premature senescence onset. It is unclear why specifically the shortest telomeres are targeted for HDR. We demonstrate that the non-coding RNA TERRA accumulates as HDR-promoting RNA-DNA hybrids (R-loops) preferentially at very short telomeres. The increased level of TERRA and R-loops, exclusively at short telomeres, is due to a local defect in RNA degradation by the Rat1 and RNase H2 nucleases, respectively...
June 29, 2017: Cell
https://www.readbyqxmd.com/read/28663070/poetry-in-motion-increased-chromosomal-mobility-after-dna-damage
#16
REVIEW
Michael J Smith, Rodney Rothstein
Double-strand breaks (DSBs) are among the most lethal DNA lesions, and a variety of pathways have evolved to manage their repair in a timely fashion. One such pathway is homologous recombination (HR), in which information from an undamaged donor site is used as a template for repair. Although many of the biochemical steps of HR are known, the physical movements of chromosomes that must underlie the pairing of homologous sequence during mitotic DSB repair have remained mysterious. Recently, several groups have begun to use a variety of genetic and cell biological tools to study this important question...
June 9, 2017: DNA Repair
https://www.readbyqxmd.com/read/28646552/targeting-histone-deacetylase-4-ubc9-impairs-dna-repair-for-radiosensitization-of-hepatocellular-carcinoma-cells
#17
Chiao-Ling Tsai, Wei-Lin Liu, Feng-Ming Hsu, Po-Sheng Yang, Ruoh-Fang Yen, Kai-Yuan Tzen, Ann-Lii Cheng, Pei-Jer Chen, Jason Chia-Hsien Cheng, Hsien Cheng
Several strategies to improve the efficacy of radiation therapy against hepatocellular carcinoma (HCC) have been investigated. One approach was to develop radiosensitizing compounds. Because histone deacetylase 4 (HDAC4) is highly expressed in liver cancer and known to regulate oncogenesis through chromatin structure remodeling and controlling protein access to DNA, we postulated that HDAC4 inhibition might enhance radiation's effect on HCC cells. HCC cell lines (Huh7 and PLC5) and an ectopic xenograft were pretreated with HDAC inhibitor or shRNA to knock down expression of HDAC4, and then irradiated (2...
June 23, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28646528/genetic-variants-in-microrna-binding-sites-of-dna-repair-genes-as-predictors-of-recurrence-in-patients-with-squamous-cell-carcinoma-of-the-oropharynx
#18
Lijun Zhu, Erich M Sturgis, Hua Zhang, Zhongming Lu, Ye Tao, Qingyi Wei, Guojun Li
The incidence of squamous cell carcinoma of the oropharynx (SCCOP) continues to rise because of increasing rates of human papillomavirus (HPV) infection. Inherited polymorphisms in DNA repair pathways may influence the risk of SCCOP development and the prognosis of SCCOP. We sought to determine whether polymorphisms in microRNA (miRNA)-binding sites within 3'-untranslated regions (3'UTRs) of genes in DNA repair pathways modulate the risk of SCCOP recurrence. We evaluated the associations between nine such polymorphisms and SCCOP recurrence in 1008 patients with incident SCCOP using the log-rank test and multivariable Cox models...
June 24, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28645374/reconstituted-system-for-the-examination-of-repair-dna-synthesis-in-homologous-recombination
#19
Youngho Kwon, James M Daley, Patrick Sung
In homologous recombination (HR), DNA polymerase δ-mediated DNA synthesis occurs within the displacement loop (D-loop) that is made by the recombinase Rad51 in conjunction with accessory factors. We describe in this chapter the reconstitution of the D-loop and repair DNA synthesis reactions using purified Saccharomyces cerevisiae HR (Rad51, RPA, and Rad54) and DNA replication (PCNA, RFC, and DNA polymerase δ) proteins and document the role of the Pif1 helicase in DNA synthesis via a migrating DNA bubble intermediate...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28640935/additive-effect-of-radiosensitization-by-2-deoxy-d-glucose-delays-dna-repair-kinetics-and-suppresses-cell-proliferation-in-oral-squamous-cell-carcinoma
#20
Mayumi Kawata, Kazuhiro Ogi, Koyo Nishiyama, Sho Miyamoto, Takafumi Nakagaki, Makoto Shimanishi, Akihiro Miyazaki, Hiroyoshi Hiratsuka
BACKGROUND: It has well known that, compared to normal cells, tumor cells have a different manner of energy metabolism, which influences the sensitivity of radiotherapy (RT). However, whether inhibition of glycolysis enhances the efficacy of radiotherapy is a matter of debate in oral squamous cell carcinoma (OSCC). The aim of this study was to characterize whether the combination of radiotherapy with the glucose inhibitor 2-deoxy-D-glucose (2-DG) affected DNA repair kinetics. METHODS: To compare the synergistic effect of 2-DG, we examined the cell survival after treatment with radiation, 2-DG and a combination of the two in 5 OSCC cell lines and one lip fibroblast cell line, determined using clonogenic survival assay...
June 22, 2017: Journal of Oral Pathology & Medicine
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