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Homologous recombination

Priyanka Sharma
Triple-negative breast cancer (TNBC) accounts for 15% of all breast cancers and is associated with poor long-term outcomes compared to other breast cancer subtypes. Currently, chemotherapy remains the main modality of treatment for early-stage TNBC, as there is no approved targeted therapy for this subtype. The biologic heterogeneity of TNBC has hindered the development and evaluation of novel agents, but recent advancements in subclassifying TNBC have paved the way for further investigation of more effective systemic therapies, including cytotoxic and targeted agents...
April 14, 2018: Current Treatment Options in Oncology
Jérôme Loc'h, Marc Delarue
Terminal deoxynucleotidyltransferase (TdT) is a member of the polX family which is involved in DNA repair. It has been known for years as an untemplated DNA polymerase used during V(D)J recombination to generate diversity at the CDR3 region of immunoglobulins and T-cell receptors. Recently, however, TdT was crystallized in the presence of a complete DNA synapsis made of two double-stranded DNA (dsDNA), each with a 3' protruding end, and overlapping with only one micro-homology base-pair, thus giving structural insight for the first time into DNA synthesis across strands...
April 12, 2018: Current Opinion in Structural Biology
Guoling Li, Dewu Liu, Xianwei Zhang, Rong Quan, Cuili Zhong, Jianxin Mo, Yaoqiang Huang, Haoqiang Wang, Xiaofang Ruan, Zheng Xu, Enqin Zheng, Ting Gu, Linjun Hong, Zicong Li, Zhenfang Wu, Huaqiang Yang
The main DNA repair pathways, nonhomologous end joining (NHEJ) and homology-directed repair (HDR), are complementary to each other; hence, interruptions of the NHEJ pathway can favor HDR. Improving HDR efficiency in animal primary fibroblasts can facilitate the generation of gene knock-in animals with agricultural and biomedical values by somatic cell nuclear transfer. In this study, we used siRNA to suppress the expression of Ku70 and Ku80, which are the key factors in NHEJ pathway, to investigate the effect of Ku silencing on the HDR efficiency in pig fetal fibroblasts...
April 12, 2018: International Journal of Biochemistry & Cell Biology
Ping Xie
The Escherichia coli RecBCD enzyme is a heterotrimeric helicase-nuclease complex responsible for processing of double-stranded DNA breaks for repair by homologous recombination. It is a highly processive, duplex unwinding and degrading motor, with its activities being regulated by the octameric recombination hotspot, Chi, which is read as a single-stranded DNA sequence. Here, a model is presented for DNA unwinding by the RecBCD complex and its regulation by Chi recognition. With the model we study analytically the dynamics of DNA unwinding of both wild-type RecBCD and mutant RecBCDK177Q with the motor function of RecD being inactivated by mutagenesis, giving quantitative explanations of the available single-molecule experimental data...
April 12, 2018: Journal of Theoretical Biology
Zijun Zhao, Mingzhang Rao, Ming Liao, Weisheng Cao
In recent years, cases of avian leukosis virus (ALV) infection have become more frequent in China. We isolated 6 ALV strains from yellow feather broiler breeders in south China from 2014 to 2016. Their full genomes were sequenced, compared, and analyzed with other reference strains of ALV. The complete genomic nucleotide sequences of GD150509, GD160403, GD160607, GDFX0601, and GDFX0602 were 7482 bp in length, whereas GDFX0603 was 7480 bp. They shared 99.7% to 99.8% identity with each other. Homology analysis showed that the gag , pol , long terminal repeats (LTRs), and the transmembrane region (gp37) of the env genes of the 6 viruses were well conserved to endogenous counterpart sequences (>97...
April 13, 2018: Viruses
Fang-Fang Jia, Hui-Qi Zheng, Si-Rui Sun, Xue-Hui Pang, Yu Liang, Jia-Cui Shang, Zong-Tao Zhu, Xiang-Chen Meng
Lactobacillus plantarum , a probiotic, has a high survival rate and high colonization ability in the gastrointestinal tract. Tolerance to the gastrointestinal environment and adhesion to intestinal epithelial cells by some Lactobacillus species (excluding L. plantarum ) are related to luxS /AI-2. Here, the role of luxS in tolerance to simulated digestive juice (SDJ) and adhesion to Caco-2 cells by L. plantarum KLDS1.0391 (hereafter, KLDS1.0391) was investigated. The KLDS1.0391 luxS mutant strain was constructed by homologous recombination...
2018: BioMed Research International
Qing Zhao, Biao Wu, Zhihong Liu, Xiujun Sun, Liqing Zhou, Aiguo Yang, Gaowei Zhang
Hemoglobin, the main component of haemolymph, is widely distributed in animals. Although its important oxygen transport functions has been extensively reported, studies on the immune function of hemoglobin in mollusc are few. Research on immune of hemoglobin of ark shell Scapharca broughtonii attracted more and more attention due to its ownership of erythrocyte comparing with many other shellfish. In this study, the hemoglobin cDNA of S. broughtonii was cloned by EST and RACE methods (named as SbHb). Sequence analysis revealed that the cDNA was 946 bp in length, including an open reading frame (ORF) of 459 bp which encoded a polypeptide of 152 amino acid residues, and a 5'-untranslated region (UTR) of 313 bp, a 3'-UTR of 174 bp...
April 9, 2018: Fish & Shellfish Immunology
Ying Zhang, Jin Guo, Li He, Hong-Ying Zong, Guo-Bin Cai
Serine proteinase inhibitor (Serpin, SPI) is a vital superfamily of endogenous inhibitors that monitor proteolytic events active in a number of biological functions. In this study, we isolated a full length gene encoding a novel serine protease inhibitor of Schistosoma japonicum (SjSPI) and characterized its molecular properties. Our result showed that SjSPI contained an open reading frame of 1,218 bp, which encoded 405 amino acid residues. Chromosomal structure analysis showed that SjSPI gene was comprised of six exons separated by five introns...
April 9, 2018: Parasitology International
Alexandra S Zimmer, Mitchell Gillard, Stanley Lipkowitz, Jung-Min Lee
The single agent activity of PARP inhibitors (PARPi) in germline BRCA mutated (gBRCAm) breast and ovarian cancer suggests untapped potential for this new class of drug in breast cancer. The US Food and Drug Administration has approved three PARPi (olaparib, rucaparib, and niraparib) so far to treat certain ovarian cancers, including those with gBRCAm and olaparib for treatment of gBRCAm breast cancers. Several PARPi are now under clinical development for breast cancer in the various treatment settings. Recently, two phase III trials of olaparib (OlympiaD) and talazoparib (EMBRACA) demonstrated 3-month progression-free survival improvement with PARPi compared to physician's choice single agent chemotherapy in metastatic gBRCAm breast cancer...
April 11, 2018: Current Treatment Options in Oncology
Qian M Cao, Yan-Yan Ni, Dianjun Cao, Debin Tian, Danielle M Yugo, C Lynn Heffron, Christopher Overend, Sakthivel Subramaniam, Adam J Rogers, Nicholas Catanzaro, Tanya LeRoith, Paul C Roberts, Xiang-Jin Meng
Cytokines are often used as adjuvants to improve vaccine immunogenicity, since they are important in initiating and shaping the immune response. The available commercial modified live-attenuated vaccines (MLVs) against porcine reproductive and respiratory syndrome virus (PRRSV) are unable to mount sufficient heterologous protection, as they typically induce weak innate and inadequate T cell responses. In this study, we investigated the immunogenicity and vaccine efficacy of recombinant PRRSV MLVs incorporated with porcine cytokine IL-15 or IL-18 gene fusing to a glycophosphatidylinositol (GPI) modification signal that can anchor the cytokines to cell membrane...
April 11, 2018: Journal of Virology
Julia M Minina, Tatjana V Karamysheva, Nicolaj B Rubtsov, Natalia S Zhdanova
Previously, we described the unique feature of telomeric regions in Iberian shrew Sorex granarius: its telomeres have two ranges of size, very small (3.8 kb of telomeric repeats on average) and very large discontinuous telomeres (213 kb) interrupted with 18S rDNA. In this study, we have demonstrated extraordinary replication pattern of S. granarius large telomeres that have not been shown before in other studied mammal. Using the ReD-FISH procedure, we observed prolonged, through S period, large telomere replication...
April 7, 2018: Protoplasma
Cheng-Yu Tsai, Si Sun, Hongying Zhang, Andrea Local, Yongxuan Su, Larry A Gross, William G Rice, Stephen B Howell
APTO-253 is a small molecule with anti-proliferative activity against cell lines derived from a wide range of human malignancies. We sought to determine the mechanisms of action and basis for resistance to APTO-253 so as to identify synthetic lethal interactions that can guide combination studies. The cellular pharmacology of APTO-253 was analyzed in Raji lymphoma cells and a subline selected for resistance (Raji/253R). Using LC/MS/ESI analysis, APTO-253 was found to convert intracellularly to a complex containing one molecule of iron and three molecules of APTO-253 [Fe(253)3]...
April 6, 2018: Molecular Cancer Therapeutics
L A Zinovkina
Accumulation of mutations in mitochondrial DNA leads to the development of severe, currently untreatable diseases. The contribution of these mutations to aging and progress of neurodegenerative diseases is actively studied. Elucidation of DNA repair mechanisms in mitochondria is necessary for both developing approaches to the therapy of diseases caused by mitochondrial mutations and understanding specific features of mitochondrial genome functioning. Mitochondrial DNA repair systems have become a subject of extensive studies only in the last decade due to development of molecular biology methods...
March 2018: Biochemistry. Biokhimii︠a︡
Lichun Tang, Yanting Zeng, Xuewei Zhou, Hongzi Du, Chuang Li, Jianqiao Liu, Pumin Zhang
Ma et al. published data in Nature Journal using human zygotes that showed that double-strand breaks (DSBs) generated by CRISPR/Cas9 could be repaired by homology-directed repair (HDR) using the wild-type allele as a template, by inter-homologue recombination (Ma et al., 2017). This result received great attention from the scientific community, however, in a recent publication, researchers have raised some concerns about Ma's interpretation of their results (Egli et al., 2017). Our previous work showed that ssODN-mediated HDR could repair 75% of DSBs generated by CRISPR/Cas9 at G6PD mutant alleles (Tang et al...
April 6, 2018: Molecular Reproduction and Development
Piotr M Skowron, Andrew M Kropinski, Joanna Zebrowska, Lukasz Janus, Kasjan Szemiako, Edyta Czajkowska, Natalia Maciejewska, Malgorzata Skowron, Joanna Łoś, Marcin Łoś, Agnieszka Zylicz-Stachula
Bacteriophage TP-84 is a well-characterized bacteriophage of historical interest. It is a member of the Siphoviridae, and infects a number of thermophilic Geobacillus (Bacillus) stearothermophilus strains. Its' 47.7-kbp double-stranded DNA genome revealed the presence of 81 coding sequences (CDSs) coding for polypeptides of 4 kDa or larger. Interestingly, all CDSs are oriented in the same direction, pointing to a dominant transcription direction of one DNA strand. Based on a homology search, a hypothetical function could be assigned to 31 CDSs...
2018: PloS One
Cyril Charbonnel, Oleh Rymarenko, Olivier Da Ines, Fatiha Benyahya, Charles I White, Falk Butter, Simon Amiard
Despite intensive searches, few proteins involved in telomere homeostasis have been identified in plants. Here, we used pull-down assays to identify potential telomeric interactors in the model plant species Arabidopsis (Arabidopsis thaliana). We identified the candidate protein GH1-HMGA1 (also known as HON4), an uncharacterised linker histone protein of the high mobility group protein A (HMGA) family in plants. HMGAs are architectural transcription factors and have been suggested to function in DNA damage repair, but their precise biological roles remain unclear...
April 5, 2018: Plant Physiology
Waqar Islam
Efficient plant genome editing is dependent upon induction of double stranded DNA breaks (DSBs) through site specified nucleases. These DSBs initiate the process of DNA repair which can either base upon homologous recombination (HR) or non-homologous end jointing (NHEJ). Recently, CRISPR-Cas9 mechanism got highlighted as revolutionizing genetic tool due to its simpler frame work along with the broad range of adaptability and applications. So, in this review, we have tried to sum up the application of this biotechnological tool in plant genome editing...
April 2, 2018: Molecular and Cellular Probes
Sarah M Misenko, Dharm S Patel, Joonyoung Her, Samuel F Bunting
'BRCAness' is a term used to describe cancer cells that behave similarly to tumors with BRCA1 or BRCA2 mutations. The BRCAness phenotype is associated with hypersensitivity to chemotherapy agents including PARP inhibitors, which are a promising class of recently-licensed anti-cancer treatments. This hypersensitivity arises because of a deficiency in the homologous recombination (HR) pathway for DNA double-strand break repair. To gain further insight into how genetic modifiers of HR contribute to the BRCAness phenotype, we created a new mouse model of BRCAness by generating mice that are deficient in BLM helicase and the Exo1 exonuclease, which are involved in the early stages of HR...
April 5, 2018: Cell Cycle
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
Wei Li, Yi Bing Ma, Ying Qiu Mao, Tong Lin
Dehydrocostus lactone is considered to be the major cholagogic ingredient of the Costus genus of plants. It exhibits strong cholagogic effects, and also exerts antimicrobial and antineoplastic activity. The present study aimed to investigate the effects of dehydrocostus lactone on the cell growth and apoptosis of recombinant human papilloma virus (HPV)‑18 HaCaT cells. The HPV‑18 genome was transfected into HaCaT cells, which were subsequently used for analysis. The results demonstrated that dehydrocostus lactone reduced the cell proliferation and induced apoptosis of HPV‑18 HaCaT cells, as determined by MTT and N‑acetyl‑Asp‑Glu‑Val‑Asp p‑nitroanilide assays, respectively...
March 28, 2018: Molecular Medicine Reports
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