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https://www.readbyqxmd.com/read/28094292/chromatin-organization-revealed-by-nanostructure-of-irradiation-induced-%C3%AE-h2ax-53bp1-and-rad51-foci
#1
Judith Reindl, Stefanie Girst, Dietrich W M Walsh, Christoph Greubel, Benjamin Schwarz, Christian Siebenwirth, Guido A Drexler, Anna A Friedl, Günther Dollinger
The spatial distribution of DSB repair factors γH2AX, 53BP1 and Rad51 in ionizing radiation induced foci (IRIF) in HeLa cells using super resolution STED nanoscopy after low and high linear energy transfer (LET) irradiation was investigated. 53BP1 and γH2AX form IRIF with same mean size of (540 ± 40) nm after high LET irradiation while the size after low LET irradiation is significantly smaller. The IRIF of both repair factors show nanostructures with partial anti-correlation. These structures are related to domains formed within the chromatin territories marked by γH2AX while 53BP1 is mainly situated in the perichromatin region...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28090586/holliday-junction-trap-shows-how-cells-use-recombination-and-a-junction-guardian-role-of-recq-helicase
#2
Jun Xia, Li-Tzu Chen, Qian Mei, Chien-Hui Ma, Jennifer A Halliday, Hsin-Yu Lin, David Magnan, John P Pribis, Devon M Fitzgerald, Holly M Hamilton, Megan Richters, Ralf B Nehring, Xi Shen, Lei Li, David Bates, P J Hastings, Christophe Herman, Makkuni Jayaram, Susan M Rosenberg
DNA repair by homologous recombination (HR) underpins cell survival and fuels genome instability, cancer, and evolution. However, the main kinds and sources of DNA damage repaired by HR in somatic cells and the roles of important HR proteins remain elusive. We present engineered proteins that trap, map, and quantify Holliday junctions (HJs), a central DNA intermediate in HR, based on catalytically deficient mutant RuvC protein of Escherichia coli. We use RuvCDefGFP (RDG) to map genomic footprints of HR at defined DNA breaks in E...
November 2016: Science Advances
https://www.readbyqxmd.com/read/28079255/moonlighting-at-replication-forks-a-new-life-for-homologous-recombination-proteins-brca1-brca2-and-rad51
#3
REVIEW
Arun Mouli Kolinjivadi, Vincenzo Sannino, Anna de Antoni, Hervé Técher, Giorgio Baldi, Vincenzo Costanzo
Coordination between DNA replication and DNA repair ensures maintenance of genome integrity, which is lost in cancer cells. Emerging evidence has linked Homologous Recombination (HR) proteins RAD51, BRCA1 and BRCA2 to the stability of nascent DNA. This function appears to be distinct from Double Strand Break (DSB) repair and is in part due to the prevention of MRE11-mediated degradation of nascent DNA at stalled forks. The role of RAD51 in fork protection resembles the activity described for its prokaryotic ortholog RecA, which prevents nuclease-mediated degradation of DNA and promotes replication fork restart in cells challenged by DNA damaging agents...
January 12, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28076794/brca1-directs-the-repair-pathway-to-homologous-recombination-by-promoting-53bp1-dephosphorylation
#4
Mayu Isono, Atsuko Niimi, Takahiro Oike, Yoshihiko Hagiwara, Hiro Sato, Ryota Sekine, Yukari Yoshida, Shin-Ya Isobe, Chikashi Obuse, Ryotaro Nishi, Elena Petricci, Shinichiro Nakada, Takashi Nakano, Atsushi Shibata
BRCA1 promotes homologous recombination (HR) by activating DNA-end resection. By contrast, 53BP1 forms a barrier that inhibits DNA-end resection. Here, we show that BRCA1 promotes DNA-end resection by relieving the 53BP1-dependent barrier. We show that 53BP1 is phosphorylated by ATM in S/G2 phase, promoting RIF1 recruitment, which inhibits resection. 53BP1 is promptly dephosphorylated and RIF1 released, despite remaining unrepaired DNA double-strand breaks (DSBs). When resection is impaired by CtIP/MRE11 endonuclease inhibition, 53BP1 phosphorylation and RIF1 are sustained due to ongoing ATM signaling...
January 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28076755/rad51-is-a-selective-dna-repair-target-to-radiosensitize-glioma-stem-cells
#5
Harry O King, Tim Brend, Helen L Payne, Alexander Wright, Thomas A Ward, Karan Patel, Teklu Egnuni, Lucy F Stead, Anjana Patel, Heiko Wurdak, Susan C Short
Patients with glioblastoma die from local relapse despite surgery and high-dose radiotherapy. Resistance to radiotherapy is thought to be due to efficient DNA double-strand break (DSB) repair in stem-like cells able to survive DNA damage and repopulate the tumor. We used clinical samples and patient-derived glioblastoma stem cells (GSCs) to confirm that the DSB repair protein RAD51 is highly expressed in GSCs, which are reliant on RAD51-dependent DSB repair after radiation. RAD51 expression and RAD51 foci numbers fall when these cells move toward astrocytic differentiation...
January 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28071676/transcriptome-analysis-of-neo-tetraploid-rice-reveals-specific-differential-gene-expressions-associated-with-fertility-and-heterosis
#6
Haibin Guo, Jean Nestor Mendrikahy, Lei Xie, Junfeng Deng, Zijun Lu, Jinwen Wu, Xiang Li, Muhammad Qasim Shahid, Xiangdong Liu
Polyploid rice hybrids have a powerful biological and yield potential that may become a new way for rice breeding; however, low fertility is major hindrance in commercial utilization. Here, we developed a neo-tetraploid rice that could overcome the sterility of autotetraploid rice and produce high heterosis. Transcriptome analysis of F1 hybrid developed by crossing neo-tetraploid with autotetraploid rice displayed 807, 663 and 866 differentially expressed genes that uniquely associated with F1 and specific to (DEGFu-sp) anther, ovary and leaf, respectively...
January 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28062703/tas-116-a-novel-hsp90-inhibitor-selectively-enhances-radiosensitivity-of-human-cancer-cells-to-x-rays-and-carbon-ion-radiation
#7
Younghyun Lee, Shigeaki Sunada, Hirokazu Hirakawa, Akira Fujimori, Jac A Nickoloff, Ryuichi Okayasu
Hsp90 inhibitors have been investigated as cancer therapeutics in monotherapy and to augment radiotherapy; however, serious adverse effects of early-generation Hsp90 inhibitors limited their development. TAS-116 is a novel Hsp90 inhibitor with lower adverse effects than other Hsp90 inhibitors, and here, we investigated the radiosensitizing effects of TAS-116 in low linear energy transfer (LET) X-ray and high LET carbon ion-irradiated human cancer cells and mouse tumor xenografts. TAS-116 decreased cell survival of both X-ray and carbon ion-irradiated human cancer cell lines (HeLa and H1299 cells), and similar to other Hsp90 inhibitors, it did not affect radiosensitivity of noncancerous human fibroblasts...
January 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28062035/single-stranded-dna-curtains-for-studying-homologous-recombination
#8
C J Ma, J B Steinfeld, E C Greene
Homologous recombination is an important pathway involved in the repair of double-stranded DNA breaks. Genetic studies form the foundation of our knowledge on homologous recombination. Significant progress has also been made toward understanding the biochemical and biophysical properties of the proteins, complexes, and reaction intermediates involved in this essential DNA repair pathway. However, heterogeneous or transient recombination intermediates remain extremely difficult to assess through traditional ensemble methods, leaving an incomplete mechanistic picture of many steps that take place during homologous recombination...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28058814/overexpression-of-tnks1bp1-in-lung-cancers-and-its-involvement-in-homologous-recombination-pathway-of-dna-double-strand-breaks
#9
Wei Tan, Hua Guan, Lian-Hong Zou, Yu Wang, Xiao-Dan Liu, Wei-Qing Rang, Ping-Kun Zhou, Hua-Dong Pei, Cai-Gao Zhong
TNKS1BP1 is a member of the poly(ADP-ribose) polymerase (PARP) superfamily. Our previous studies have demonstrated that TNKS1BP1 plays an important role in DNA damage response. But whether and how TNKS1BP1 associates with cancer is still not clear. Here, we found that TNKS1BP1 was upregulated in human lung adenocarcinoma (LAC) tissues, and was associated with poor overall survival (OS) in LAC patients. Dysregulation of TNKS1BP1 affected the sensitivity of A549 cells to several DNA damage agents including cisplatin, bleomycin, and ionizing radiation...
January 6, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28058614/simultaneous-atm-brca1-rad51-expression-variations-associated-with-prognostic-factors-in-iranian-sporadic-breast-cancer-patients
#10
Zeinab Hallajian, Frouzandeh Mahjoubi, Nahid Nafissi
BACKGROUND: DNA double-strand breaks (DSBs) as a serious lesion are repaired by non-homologous end-joining and homologous recombination pathways. ATM, BRCA1, RAD51 genes are involved in HR pathways. While some studies have revealed individual expression changes of these genes in different types of cancer, there are limited studies attempting to evaluate correlation of expression variations of these genes in breast cancer pathogenesis. This study aimed to determine RAD51, ATM and BRCA1 gene expression level and its association with clinicopathological factors in fresh breast cancer tissues...
January 5, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/28058502/a-novel-loss-of-function-heterozygous-brca2-c-8946_8947delag-mutation-found-in-a-chinese-woman-with-family-history-of-breast-cancer
#11
Jing Ma, Jichun Yang, Wenjing Jian, Xianming Wang, Deyong Xiao, Wenjun Xia, Likuan Xiong, Duan Ma
INTRODUCTION: Breast cancer is the most frequent female malignancy worldwide. Among them, some cases have hereditary susceptibility in two leading genes, BRCA1 and BRCA2. Heterozygous germ line mutations in them are related with increased risk of breast, ovarian and other cancer, following autosomal dominant inheritance mode. METHODS AND RESULTS: For purpose of early finding, early diagnosis and early treatment, mutation detecting of BRCA1/2 genes was performed in unselected 300 breast or ovarian patients and unaffected women using next-generation sequencing and then confirmed by Sanger sequencing...
January 5, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28057929/a-novel-role-for-the-dna-repair-gene-rad51-in-netrin-1-signalling
#12
K A Glendining, D Markie, R J M Gardner, E A Franz, S P Robertson, C L Jasoni
Mutations in RAD51 have recently been linked to human Congenital Mirror Movements (CMM), a developmental disorder of the motor system. The only gene previously linked to CMM encodes the Netrin-1 receptor DCC, which is important for formation of corticospinal and callosal axon tracts. Thus, we hypothesised that Rad51 has a novel role in Netrin-1-mediated axon development. In mouse primary motor cortex neurons, Rad51 protein was redistributed distally down the axon in response to Netrin-1, further suggesting a functional link between the two...
January 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28046023/a-model-to-investigate-single-strand-dna-responses-in-g1-human-cells-via-a-telomere-targeted-nuclease-deficient-crispr-cas9-system
#13
Remco P Crefcoeur, Omar Zgheib, Thanos D Halazonetis
DNA replication stress has the potential to compromise genomic stability and, therefore, cells have developed elaborate mechanisms to detect and resolve problems that may arise during DNA replication. The presence of single-stranded DNA (ssDNA) is often associated with DNA replication stress and serves as a signal for both checkpoint and repair responses. In this study, we exploited a CRISPR-Cas9 system to induce regions of ssDNA in the genome. Specifically, single-guide RNAs bearing sequence complementarity to human telomeric repeats, were used to target nuclease-deficient Cas9 (dCas9) to telomeres...
2017: PloS One
https://www.readbyqxmd.com/read/28034904/rad51-mediates-resistance-of-cancer-stem-cells-to-parp-inhibition-in-triple-negative-breast-cancer
#14
Yajing Liu, Monika L Burness, Rachel Martin-Trevino, Joey Guy, Shoumin Bai, Ramdane Harouaka, Michael D Brooks, Li Shang, Alex Fox, Tahra K Luther, April Davis, Trenton L Baker, Justin Colacino, Shawn G Clouthier, Zhi-Ming Shao, Max S Wicha, Suling Liu
INTRODUCTION: PARP inhibitors have shown promising results in early studies for treatment of breast cancer susceptibility gene (BRCA)-deficient breast cancers; however, resistance ultimately develops. Furthermore, the benefit of PARP inhibitors (PARPi) in triple-negative breast cancers (TNBC) remains unknown. Recent evidence indicates that in TNBCs, cells that display "cancer stem cell" properties are resistant to conventional treatments, mediate tumor metastasis, and contribute to recurrence...
December 29, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28030834/histone-deacetylases-1-and-2-cooperate-in-regulating-brca1-chk1-and-rad51-expression-in-acute-myeloid-leukemia-cells
#15
Jianyun Zhao, Chengzhi Xie, Holly Edwards, Guan Wang, Jeffrey W Taub, Yubin Ge
Resistance to chemotherapy and a high relapse rate highlight the importance of finding new therapeutic options for the treatment of acute myeloid leukemia (AML). Histone deacetylase (HDAC) inhibitors (HDACIs) are a promising class of drugs for the treatment of AML. HDACIs have limited single-agent clinical activities, but when combined with conventional or investigational drugs they have demonstrated favorable outcomes. Previous studies have shown that decreasing expression of important DNA damage repair proteins enhances standard chemotherapy drugs...
December 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/28028228/large-scale-heterochromatin-remodeling-linked-to-overreplication-associated-dna-damage
#16
Wei Feng, Christopher J Hale, Ryan S Over, Shawn J Cokus, Steven E Jacobsen, Scott D Michaels
Previously, we have shown that loss of the histone 3 lysine 27 (H3K27) monomethyltransferases ARABIDOPSIS TRITHORAX-RELATED 5 (ATXR5) and ATXR6 (ATXR6) results in the overreplication of heterochromatin. Here we show that the overreplication results in DNA damage and extensive chromocenter remodeling into unique structures we have named "overreplication-associated centers" (RACs). RACs have a highly ordered structure with an outer layer of condensed heterochromatin, an inner layer enriched in the histone variant H2AX, and a low-density core containing foci of phosphorylated H2AX (a marker of double-strand breaks) and the DNA-repair enzyme RAD51...
December 27, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28027876/ercc2-xpd-lys751gln-alter-dna-repair-efficiency-of-platinum-induced-dna-damage-through-p53-pathway
#17
Guopei Zhang, Yangyang Guan, Yuejiao Zhao, Tahar van der Straaten, Sha Xiao, Ping Xue, Guolian Zhu, Qiufang Liu, Yuan Cai, Cuihong Jin, Jinghua Yang, Shengwen Wu, Xiaobo Lu
Platinum-based treatment causes Pt-DNA adducts which lead to cell death. The platinum-induced DNA damage is recognized and repaired by the nucleotide excision repair (NER) system of which ERCC2/XPD is a critical enzyme. Single nucleotide polymorphisms in ERCC2/XPD have been found to be associated with platinum resistance. The aim of the present study was to investigate whether ERCC2/XPD Lys751Gln (rs13181) polymorphism is causally related to DNA repair capacity of platinum-induced DNA damage. First, cDNA clones expressing different genotypes of the polymorphism was transfected to an ERCC2/XPD defective CHO cell line (UV5)...
December 24, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28018950/data-on-rad51-amino-acid-sequences-from-higher-and-lower-eukaryotic-model-organisms-and-parasites
#18
Andrew A Kelso, Steven D Goodson, Lesly A Temesvari, Michael G Sehorn
This paper contains data related to the research article titled "Characterization of the recombination activities of the Entamoeba histolytica Rad51 recombinase" (Kelso et al., in press) [1]. The known and putative amino acid sequence of Rad51, the central enzyme of homologous recombination, from nineteen different higher and lower eukaryotic organisms was analyzed. Here, we show amino acid conservation using a multiple sequence alignment, overall sequence identities using a percent identity matrix, and the evolutionary relationship between organisms using a neighbor-joining tree...
February 2017: Data in Brief
https://www.readbyqxmd.com/read/28011904/multifunctional-roles-of-saccharomyces-cerevisiae-srs2-protein-in-replication-recombination-and-repair
#19
Hengyao Niu, Hannah L Klein
The Saccharomyces cerevisiae Srs2 DNA helicase has important roles in DNA replication, recombination and repair. In replication, Srs2 aids in repair of gaps by repair synthesis by preventing gaps from being used to initiate recombination. This is considered to be an anti-recombination role. In recombination, Srs2 plays both pro-recombination and anti-recombination roles to promote the synthesis-dependent strand annealing (SDSA) recombination pathway and to inhibit gaps from initiating homologous recombination (HR)...
December 23, 2016: FEMS Yeast Research
https://www.readbyqxmd.com/read/28009302/rpa-stabilization-of-single-stranded-dna-is-critical-for-break-induced-replication
#20
Patrick Ruff, Roberto A Donnianni, Eleanor Glancy, Julyun Oh, Lorraine S Symington
DNA double-strand breaks (DSBs) are cytotoxic lesions that must be accurately repaired to maintain genome stability. Replication protein A (RPA) plays an important role in homology-dependent repair of DSBs by protecting the single-stranded DNA (ssDNA) intermediates formed by end resection and by facilitating Rad51 loading. We found that hypomorphic mutants of RFA1 that support intra-chromosomal homologous recombination are profoundly defective for repair processes involving long tracts of DNA synthesis, in particular break-induced replication (BIR)...
December 20, 2016: Cell Reports
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