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https://www.readbyqxmd.com/read/29759113/distinct-roles-of-atm-and-atr-in-the-regulation-of-arp8-phosphorylation-to-prevent-chromosome-translocations
#1
Jiying Sun, Lin Shi, Aiko Kinomura, Atsuhiko Fukuto, Yasunori Horikoshi, Yukako Oma, Masahiko Harata, Masae Ikura, Tsuyoshi Ikura, Roland Kanaar, Satoshi Tashiro
Chromosomal translocations are hallmarks of various types of cancers and leukemias. However, the molecular mechanisms of chromosome translocations remain largely unknown. The ataxia-telangiectasia mutated (ATM) protein, a DNA damage signaling regulator, facilitates DNA repair to prevent chromosome abnormalities. Previously, we showed that ATM deficiency led to the 11q23 chromosome translocation, the most frequent chromosome abnormalities in secondary leukemia. Here, we show that ARP8, a subunit of the INO80 chromatin remodeling complex, is phosphorylated after etoposide treatment...
May 8, 2018: ELife
https://www.readbyqxmd.com/read/29749376/corylin-increases-the-sensitivity-of-hepatocellular-carcinoma-cells-to-chemotherapy-through-long-noncoding-rna-rad51-as1-mediated-inhibition-of-dna-repair
#2
Chin-Chuan Chen, Chi-Yuan Chen, Shir-Hwa Ueng, Chuen Hsueh, Chau-Ting Yeh, Jar-Yi Ho, Li-Fang Chou, Tong-Hong Wang
Corylin, a biologically active agent extracted from Psoralea corylifolia L. (Fabaceae), promotes bone differentiation and inhibits inflammation. Currently, few reports have addressed the biological functions that are regulated by corylin, and to date, no studies have investigated its antitumor activity. In this study, we used cell functional assays to analyze the antitumor activity of corylin in hepatocellular carcinoma (HCC). Furthermore, whole-transcriptome assays were performed to identify the downstream genes that were regulated by corylin, and gain-of-function and loss-of-function experiments were conducted to examine the regulatory roles of the above genes...
May 10, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29740405/sak4-of-phage-hk620-is-a-reca-remote-homolog-with-single-strand-annealing-activity-stimulated-by-its-cognate-ssb-protein
#3
Geoffrey Hutinet, Arthur Besle, Olivier Son, Stephen McGovern, Raphaël Guerois, Marie-Agnès Petit, Françoise Ochsenbein, François Lecointe
Bacteriophages are remarkable for the wide diversity of proteins they encode to perform DNA replication and homologous recombination. Looking back at these ancestral forms of life may help understanding how similar proteins work in more sophisticated organisms. For instance, the Sak4 family is composed of proteins similar to the archaeal RadB protein, a Rad51 paralog. We have previously shown that Sak4 allowed single-strand annealing in vivo , but only weakly compared to the phage λ Redβ protein, highlighting putatively that Sak4 requires partners to be efficient...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29735283/break-induced-replication-the-where-the-why-and-the-how
#4
REVIEW
J Kramara, B Osia, A Malkova
Break-induced replication (BIR) is a pathway that repairs one-ended double-strand breaks (DSBs). For decades, yeast model systems offered the only opportunities to study eukaryotic BIR. These studies described an unusual mode of BIR synthesis that is carried out by a migrating bubble and shows conservative inheritance of newly synthesized DNA, leading to genomic instabilities like those associated with cancer in humans. Yet, evidence of BIR functioning in mammals or during repair of other DNA breaks has been missing...
May 4, 2018: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/29731985/association-between-homologous-recombination-repair-gene-mutations-and-response-to-oxaliplatin-in-pancreatic-cancer
#5
Tomohiro Kondo, Masashi Kanai, Tadayuki Kou, Tomohiro Sakuma, Hiroaki Mochizuki, Mayumi Kamada, Masahiko Nakatsui, Norimitsu Uza, Yuzo Kodama, Toshihiko Masui, Kyoichi Takaori, Shigemi Matsumoto, Hidehiko Miyake, Yasushi Okuno, Manabu Muto
Objectives: We aimed to examine the association between homologous recombination repair (HRR)-related gene mutations and efficacy of oxaliplatin-based chemotherapy in patients with pancreatic ductal adenocarcinoma (PDAC). Results: Non-synonymous mutations in HRR-related genes were found in 13 patients and only one patient had a family history of pancreatic cancer. Eight patients with HRR-related gene mutations (group A) and nine without HRR-related gene mutations (group B) received oxaliplatin-based chemotherapy...
April 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29731842/effect-of-rad51c-expression-on-the-chemosensitivity-of-e%C3%AE-myc-p19-arf-cells-and-its-clinical-significance-in-breast-cancer
#6
Shao-Guang Liao, Lu Liu, Ya-Jie Wang
The aim of the present study was to investigate the chemosensitivity to anti-cancer drugs of RAD51 paralog C (RAD51C)-deficient Eμ-Myc p19Arf-/- cells, to detect the expression of RAD51C in breast cancer tissues by immunohistochemistry (IHC), and to explore their association with clinicopathological factors. Eμ-Myc p19Arf-/- cells were stably transfected with retroviruses co-expressing short hairpin-RNA against RAD51C and green fluorescent protein (GFP). A single-cell flow cytometry-based GFP competition assay was used to assess the change in sensitivity to anti-cancer drugs...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29729110/rice-rad51-paralogs-play-essential-roles-in-somatic-homologous-recombination-in-dna-repair
#7
Zhan Xu, Jianxiang Zhang, Meng Xu, Wen Ji, Meimei Yu, Yajun Tao, Zhiyun Gong, Minghong Gu, Hengxiu Yu
Synthesis-dependent strand annealing (SDSA) and single-strand annealing (SSA) are the two main homologous recombination (HR) pathways in double-strand break (DSB) repair. The involvement of rice RAD51 paralogs in HR is well known in meiosis, although the molecular mechanism in somatic HR remains obscure. Loss-of-function mutants of rad51 paralogs show increased sensitivity to the DSB-inducer bleomycin, which results in greatly compromised somatic recombination efficiencies (xrcc3 in SDSA, rad51b and xrcc2 in SSA, rad51c and rad51d in both)...
May 5, 2018: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29705126/the-mre11a470t-mutation-and-homeologous-interactions-increase-error-prone-bir
#8
In-Joon Baek, Courtney Parke, Arthur J Lustig
In the absence of the RNA-templated reverse transcriptase, telomerase, the predominant means of terminal addition, arises from break-induced replication (BIR) at multiple homologous subtelomeric Y' loci and among internal homeologous (imperfect) (polyG1-3T) tracts. These last tracts are interspersed between subtelomeric Y' direct repeats. One major survivor class contains very short (~50 bp) terminal telomere repeats. This size is sufficient for slow growth and partial telomere functionality and cell viability...
April 26, 2018: Gene
https://www.readbyqxmd.com/read/29697413/inhibition-of-fibroblast-growth-factor-receptor-signaling-sensitizes-imatinib-resistant-gastrointestinal-stromal-tumors-to-low-doses-of-topoisomerase-ii-inhibitors
#9
Sergei Boichuk, Pavel Dunaev, Aigul Galembikova, Ilshat Mustafin, Elena Valeeva
The acquired resistance of gastrointestinal stromal tumors (GISTs) to the targeted-based therapy remains the driving force to identify the novel approaches that are capable of increasing the sensitivity of GISTs to the current therapeutic regimens. Our present data show that BGJ398, a selective fibroblast growth factor receptor (FGFR) inhibitor, sensitizes imatinib (IM)-resistant GIST cells with receptor tyrosine kinase (RTK) switch (loss of c-KIT/gain of pFGFR2a) to the low doses of topoisomerase II inhibitors - doxorubicin (Dox) and etoposide (Eto)...
April 24, 2018: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29696366/genetic-interaction-between-two-insulin-dependent-diabetes-susceptibility-loci-idd2-and-idd13-in-determining-immunoregulatory-dn-t-cell-proportion
#10
Roxanne Collin, Kathy Doyon, Victor Mullins-Dansereau, Martin Karam, Geneviève Chabot-Roy, Erin E Hillhouse, Alexandre Orthwein, Sylvie Lesage
Several immune regulatory cell types participate in the protection against autoimmune diseases such as autoimmune diabetes. Of these immunoregulatory cells, we and others have shown that peripheral CD4- CD8- double negative (DN) T cells can induce antigen-specific immune tolerance. Particularly, we have described that diabetes-prone mice exhibit a lower number of peripheral DN T cells compared to diabetes-resistant mice. Identifying the molecular pathways that influence the size of the DN T cell pool in peripheral lymphoid organs may thus be of interest for maintaining antigen-specific immune tolerance...
April 25, 2018: Immunogenetics
https://www.readbyqxmd.com/read/29694959/prognostic-impact-of-dna-repair-protein-expression-in-non-small-cell-lung-cancers-treated-with-platinum-based-chemotherapy-and-subsequent-curative-lung-resection
#11
Junghoon Shin, Kyu Sang Lee, Kyung Ah Yoh, Hyun Jin Cho, Moon Ki Choi, Se Hyun Kim, Yu Jung Kim, Jin-Haeng Chung, Sukki Cho, Kwhanmien Kim, Sanghoon Jheon, Ho Il Yoon, Jae Ho Lee, Choon-Taek Lee, Jong Seok Lee
OBJECTIVE: Multimodal treatments that include preoperative platinum-based chemotherapy are fundamental to the treatment of advanced non-small cell lung cancer (NSCLC). This study aimed to investigate the predictive value of DNA repair protein expression in surgically resected NSCLCs in terms of prognosis and responses to platinum-containing chemotherapy. METHODS: This retrospective study included 136 patients with NSCLC who were treated with preoperative platinum-based chemotherapy, followed by curative lung resection...
April 25, 2018: Oncology
https://www.readbyqxmd.com/read/29681946/inhibition-of-rad51-by-sirna-and-resveratrol-sensitizes-cancer-stem-cells-derived-from-hela-cell-cultures-to-apoptosis
#12
Graciela Ruíz, Heriberto A Valencia-González, Ismael León-Galicia, Enrique García-Villa, Alejandro García-Carrancá, Patricio Gariglio
Cervical cancer is the second most frequent tumor type in women worldwide with cases developing clinical recurrence, metastasis, and chemoresistance. The cancer stem cells (CSC) may be implicated in tumor resistance to therapy. RESveratrol (RES), a natural compound, is an antioxidant with multiple beneficial activities. We previously determined that the expression of RAD51 is decreased by RES. The aim of our study was to examine molecular mechanism by which CSC from HeLa cultures exhibit chemoresistance. We hypothesized CSC repair more efficiently DNA breaks and that RAD51 plays an important role in this mechanism...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29674319/long-repeating-ttaggg-n-single-stranded-dna-self-condenses-into-compact-beaded-filaments-stabilized-by-g-quadruplex-formation
#13
Anirban Kar, Nathan Jones, N Özlem Arat, Richard Fishel, Jack Griffith
Conformations adopted by long stretches of single stranded DNA (ssDNA) are of central interest in understanding the architecture of replication forks, R loops, and other structures generated during DNA metabolism in vivo. This is particularly so if the ssDNA consists of short nucleotide repeats. Such studies have been hampered by the lack of defined substrates greater than ~150 nt, and the absence of high-resolution biophysical approaches. Here we describe the generation of very long ssDNA consisting of the mammalian telomeric repeat (5'-TTAGGG-3')n as well as the interrogation of its structure by electron microscopy (EM) and single molecule magnetic tweezers (smMT)...
April 19, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29673125/major-pathologic-response-and-rad51-predict-survival-in-lung-cancer-patients-receiving-neoadjuvant-chemotherapy
#14
Apar Pataer, Ruping Shao, Arlene M Correa, Carmen Behrens, Jack A Roth, Ara A Vaporciyan, Ignacio I Wistuba, Stephen G Swisher
In a previous study, we determined that major pathologic response (MPR) as indicated by the percentage of residual viable tumor cells predicted overall survival (OS) in patients with non-small-cell lung cancer (NSCLC) who received neoadjuvant chemotherapy. In this study, we assessed whether two genes and five protein biomarkers could predict MPR and OS in 98 patients with NSCLC receiving neoadjuvant chemotherapy. We collected formalin-fixed, paraffin-embedded specimens of resected NSCLC tumors from 98 patients treated with neoadjuvant chemotherapy...
April 19, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29670086/mir-98-5p-contributes-to-cisplatin-resistance-in-epithelial-ovarian-cancer-by-suppressing-mir-152-biogenesis-via-targeting-dicer1
#15
Yanan Wang, Wei Bao, Yuan Liu, Shiyu Wang, Shengjie Xu, Xi Li, Yanli Li, Sufang Wu
Epithelial ovarian cancer (EOC) is a highly lethal gynecological malignancy, and cisplatin resistance is usually correlated with the poor prognosis of EOC. Increasing evidence indicates that the dysregulation of miRNAs is related to chemotherapy sensitivity. In this study, we revealed that miR-98-5p, a member of the let-7 family, was enriched in cisplatin-resistant EOC cells compared with cisplatin-sensitive cells, and could promote cisplatin resistance in EOC cells. Further studies showed that miR-98-5p could directly target the 3'-UTR of Dicer1 and suppress its expression, causing global miRNA downregulation...
April 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29627753/cr-vi-induced-methylation-and-down-regulation-of-dna-repair-genes-and-its-association-with-markers-of-genetic-damage-in-workers-and-16hbe-cells
#16
Guiping Hu, Ping Li, Xiaoxing Cui, Yang Li, Ji Zhang, Xinxiao Zhai, Shanfa Yu, Shichuan Tang, Zuchang Zhao, Jing Wang, Guang Jia
To examine the mechanism of hexavalent chromium [Cr(VI)]-induced carcinogenesis, a cross-sectional study in workers with or without exposure to Cr(VI) as well as in vitro administration of Cr(VI) in 16HBE cells was conducted. We explored the associations between Cr(VI) exposure, methylation modification of DNA repair genes and their expression levels, and genetic damage. Results showed that hypermethylation of CpG sites were observed in both occupationally exposed workers and 16HBE cells administrated Cr(VI)...
April 5, 2018: Environmental Pollution
https://www.readbyqxmd.com/read/29627078/the-roles-of-jak2-in-dna-damage-and-repair-in-the-myeloproliferative-neoplasms-opportunities-for-targeted-therapy
#17
REVIEW
Theodoros Karantanos, Alison R Moliterno
The JAK2V617F-positive myeloproliferative neoplasms (MPN) serve as an excellent model for the study of genomic instability accumulation during cancer progression. Recent studies highlight the implication of JAK2 activating mutations in the development of DNA damage via reactive oxygen species (ROS) production, replication stress induction and the accumulation of genomic instability via the increased degradation of p53 and acquisition of a "mutagenic" phenotype. The accumulation of genomic instability and acquisition of mutations in critical DNA damage repair (DDR) mediators appears to be implicated in the progression of JAK2V617F-positive MPN...
March 30, 2018: Blood Reviews
https://www.readbyqxmd.com/read/29620223/resveratrol-decreases-rad51-expression-and-sensitizes-cisplatin%C3%A2-resistant-mcf%C3%A2-7-breast-cancer-cells
#18
I Leon-Galicia, J Diaz-Chavez, M E Albino-Sanchez, E Garcia-Villa, R Bermudez-Cruz, J Garcia-Mena, L A Herrera, A García-Carrancá, P Gariglio
Resveratrol (RES), a polyphenol compound with anti‑proliferative properties, has been previously evaluated for its beneficial effects against a variety of tumour cells. The current study elucidated the means by which RES enhances the anti‑proliferative effects of cisplatin (CIS) on MCF‑7 cells, focusing on the inhibitory effects on DNA repair of double‑strand breaks (DSBs). Chemoresistant MCF‑7 cells (MCF‑7R) were generated by continuous exposure to low concentrations of CIS (10 µM CIS‑IC40) during 5 passages, with the IC50 value increasing ~3‑fold...
March 27, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29619377/roles-of-nucks1-in-diseases-susceptibility-potential-biomarker-and-regulatory-mechanisms
#19
REVIEW
Pengru Huang, Yujie Cai, Bin Zhao, Lili Cui
Nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1) is a 27 kD chromosomal, highly conserved, and vertebrate-specific protein. NUCKS1 gene encodes a nuclear protein and the conserved regions of NUCKS1 contain several consensus phosphorylation sites for casein kinase II (CK2) and cyclin-dependent kinases (Cdk) and a basic DNA-binding domain. NUCKS1 is similar to the high mobility group (HMG) family which dominates chromatin remodeling and regulates gene transcription. Meanwhile, NUCKS1 is a RAD51 associated protein 1 (RAD51AP1) paralog that is significant for homologous recombination (HR) and genome stability and also a transcriptional regulator of the insulin signaling components...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29618789/altered-dna-repair-an-early-pathogenic-pathway-in-alzheimer-s-disease-and-obesity
#20
Hao Yu, Fiona Edith Harrison, Fen Xia
Unrepaired DNA double-strand breaks (DSBs) are lethal. The present study compared the extent of DSBs, neuronal apoptosis, and status of two major DSB repair pathways - homologous combinational repair (HR) and nonhomologous end-joining (NHEJ) - in hippocampus of 5-6 month and 16-18 month-old wild-type and APP/PSEN1 mice fed control diet or high fat diet (60% fat from lard). We performed immunohistochemical staining and quantification for nuclear foci formation of γ-H2AX for DSBs, RAD51, and 53BP1, which represent the functional status of HR and NHEJ, respectively...
April 4, 2018: Scientific Reports
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