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homologous dependent recombination

Vijay Jayaraman, Arpitha Suryavanshi, Pavithra Kalale, Jyothirmai Kunala, Hemalatha Balaram
Plasmodium falciparum (Pf), the causative agent of malaria, has an iron-sulfur cluster-containing class I fumarate hydratase (FH) that catalyzes the interconversion of fumarate to malate, a well-known reaction in the tricarboxylic acid cycle. In humans, the same reaction is catalyzed by class II FH that has no sequence or structural homology with the class I enzyme from Plasmodium. Fumarate is generated in large quantities in the parasite as a byproduct of AMP synthesis and is converted to malate by FH and then used in the generation of the key metabolites oxaloacetate, aspartate, and pyruvate...
February 15, 2018: Journal of Biological Chemistry
Thomas Pelz, Daniela R Drose, David Fleck, Bastian Henkel, Tobias Ackels, Marc Spehr, Eva M Neuhaus
TMEM16 proteins are a recently identified protein family comprising Ca2+-activated Cl- channels that generate outwardly rectifying ionic currents in response to intracellular Ca2+ elevations. Some TMEM16 family members, such as TMEM16F/ANO6 are also essential for Ca2+-dependent phospholipid scrambling. TMEM16-like genes are present in the genomes of most eukaryotic species, the function(s) of TMEM16 family members from evolutionary ancient eukaryotes is not completely clear. Here, we provide insight into the evolution of these TMEM16 proteins by similarity searches for ancestral sequences...
2018: PloS One
Sousuke Imamura, Yuhta Nomura, Tokiaki Takemura, Imran Pancha, Keiko Taki, Kazuki Toguchi, Yuzuru Tozawa, Kan Tanaka
Chloroplasts are plant organelles that carry out oxygenic photosynthesis. Chloroplast biogenesis depends upon chloroplast ribosomes and their translational activity. However, regulation of chloroplast ribosome biogenesis remains an important unanswered question. In this study, we found that inhibition of target of rapamycin (TOR), a general eukaryotic checkpoint kinase, results in a decline in chloroplast ribosomal RNA (rRNA) transcription in the unicellular red alga, Cyanidioschyzon merolae. Upon TOR inhibition, transcriptomics and other analyses revealed increased expression of a nuclear-encoded chloroplast RelA-SpoT homolog (RSH) gene (CmRSH4b), which encodes a homolog of the guanosine 3'-diphosphate 5'-diphosphate (ppGpp) synthetases that modulate rRNA synthesis in bacteria...
February 14, 2018: Plant Journal: for Cell and Molecular Biology
Susan E Scanlon, Denise C Hegan, Parker L Sulkowski, Peter M Glazer
The von Hippel-Lindau ( VHL ) tumor suppressor gene is inactivated in the vast majority of human clear cell renal carcinomas. The pathogenesis of VHL loss is currently best understood to occur through stabilization of the hypoxia-inducible factors, activation of hypoxia-induced signaling pathways, and transcriptional reprogramming towards a pro-angiogenic and pro-growth state. However, hypoxia also drives other pro-tumorigenic processes, including the development of genomic instability via down-regulation of DNA repair gene expression...
January 12, 2018: Oncotarget
Jung-Kuei Chen, Wen-Ling Lin, Zhang Chen, Hung-Wen Liu
Maintenance of genome integrity is critical for both faithful propagation of genetic information and prevention of mutagenesis induced by various DNA damage events. Here we report cold-inducible RNA-binding protein (CIRBP) as a newly identified key regulator in DNA double-strand break (DSB) repair. On DNA damage, CIRBP temporarily accumulates at the damaged regions and is poly(ADP ribosyl)ated by poly(ADP ribose) polymerase-1 (PARP-1). Its dissociation from the sites of damage may depend on its phosphorylation status as mediated by phosphatidylinositol 3-kinase-related kinases...
February 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
Hirokazu Yagi, Daisuke Takakura, Lubka T Roumenina, Wolf Herman Fridman, Catherine Sautès-Fridman, Nana Kawasaki, Koichi Kato
Fc-receptors for immunoglobulin G (FcγRs) mediate a variety of effector and regulatory mechanisms in the immune system. N-glycosylation of FcγRs critically affects their functions which is well exemplified by antibody-dependent cell-mediated cytotoxicity (ADCC) and phagocytosis mediated by homologous FcγRIIIa and FcγRIIIb, respectively. Although several reports describe N-glycosylation profiles of recombinant FcγRIII glycoproteins, much remains unknown regarding their native glycoforms. Here we performed site-specific N-glycosylation profiling of a soluble form of FcγRIIIb purified from human serum based on mass spectrometric analysis...
February 9, 2018: Scientific Reports
Wei-Ting Lu, Ben R Hawley, George L Skalka, Robert A Baldock, Ewan M Smith, Aldo S Bader, Michal Malewicz, Felicity Z Watts, Ania Wilczynska, Martin Bushell
The error-free and efficient repair of DNA double-stranded breaks (DSBs) is extremely important for cell survival. RNA has been implicated in the resolution of DNA damage but the mechanism remains poorly understood. Here, we show that miRNA biogenesis enzymes, Drosha and Dicer, control the recruitment of repair factors from multiple pathways to sites of damage. Depletion of Drosha significantly reduces DNA repair by both homologous recombination (HR) and non-homologous end joining (NHEJ). Drosha is required within minutes of break induction, suggesting a central and early role for RNA processing in DNA repair...
February 7, 2018: Nature Communications
Joonyoung Her, Samuel F Bunting
DNA double-strand breaks (DSBs) arise regularly in cells and when left unrepaired, cause senescence or cell death. Homologous recombination (HR) and nonhomologous end-joining (NHEJ) are the two major DNA-repair pathways. Whereas HR allows faithful DSB repair and healthy cell growth, NHEJ has higher potential to contribute to mutations and malignancy. Many regulatory mechanisms influence which of these two pathways is used in DSB repair. These mechanisms depend on the cell cycle, post-translational modifications, and chromatin effects...
February 5, 2018: Journal of Biological Chemistry
Brian Burke
Meiosis is a key processes of sexual reproduction in eukaryotes. By combining two cell division cycles with a single round of DNA replication meiosis provides a mechanism to generate haploid gametes. Coincidentally, processes involved in ensuring appropriate segregation of homologous chromosomes also result in genetic recombination and shuffling of genes between each generation. During the first meiotic prophase, rapid telomere-led chromosome movements facilitate alignment and pairing of homologous chromosomes...
January 29, 2018: Current Opinion in Cell Biology
Liangwen Chen, Huangqi Tang, Yan Du, Zhangyu Dai, Ting Wang, Lijun Wu, Libin Zhou, Po Bian
Heavy-ion radiation has attracted extensive attention as an effective cancer therapy because of the varying energy deposition along its track and its high cell-killing effect. Reproductive cell death (RCD), also known as clonogenic death, is an important mode of death of the cancer cells after radiotherapy. Although RCD induced by heavy-ion irradiation with various linear energy transfers has been demonstrated using clonogenic assay in vitro, little is known about the distribution of RCD across the range of heavy-ion irradiation at the level of whole organisms...
February 1, 2018: DNA Repair
Fabrizia Carofiglio, Esther Sleddens-Linkels, Evelyne Wassenaar, Akiko Inagaki, Wiggert A van Cappellen, J Anton Grootegoed, Attila Toth, Willy M Baarends
Repair of SPO11-dependent DNA double-strand breaks (DSBs) via homologous recombination (HR) is essential for stable homologous chromosome pairing and synapsis during meiotic prophase. Here, we induced radiation-induced DSBs to study meiotic recombination and homologous chromosome pairing in mouse meiocytes in the absence of SPO11 activity (Spo11YF/YF model), and in the absence of both SPO11 and HORMAD1 (Spo11/Hormad1 dko). Within 30 min after 5 Gy irradiation of Spo11YF/YF mice, 140-160 DSB repair foci were detected, which specifically localized to the synaptonemal complex axes...
January 31, 2018: DNA Repair
Qun Tang, Yan-Ping Liu, Hai-Huan Shan, Li-Fei Tian, Jie-Zhong Zhang, Xiao-Xue Yan
RecF is a principal member of the RecF pathway. It interacts with RecO and RecR to initiate homologous recombination by loading RecA recombinases on single-stranded DNA and displacing single-stranded DNA-binding proteins. As an ATP-binding cassette ATPase, RecF exhibits ATP-dependent dimerization and structural homology with Rad50 and SMC proteins. However, the mechanism and action pattern of RecF ATP-dependent dimerization remains unclear. Here, We determined three crystal structures of TTERecF, TTERecF-ATP and TTERecF-ATPɤS from Thermoanaerobacter tengcongensis that reveal a novel ATP-driven RecF dimerization...
February 1, 2018: Scientific Reports
Marcus Davidsson, Paula Díaz-Fernández, Marcos Torroba, Oliver D Schwich, Patrick Aldrin-Kirk, Luis Quintino, Andreas Heuer, Gang Wang, Cecilia Lundberg, Tomas Bjorklund
Genome editing has proven to be highly potent in the generation of functional gene knockouts in dividing cells. In the CNS however, efficient technologies to repair sequences are yet to materialize. Reprogramming on the mRNA level is an attractive alternative as it provides means to perform in situ editing of coding sequences without nuclease dependency. Furthermore, de novo sequences can be inserted without the requirement of homologous recombination. Such reprogramming would enable efficient editing in quiescent cells (e...
January 31, 2018: RNA
Chao-Cheng Huang, Hsiao-Mei Kuo, Pei-Chang Wu, Shih-Hsuan Cheng, Tzu-Ting Chang, Yi-Chen Chang, Mei-Lang Kung, Deng-Chyang Wu, Jiin-Haur Chuang, Ming-Hong Tai
AIM: Delta-like 1 homolog (DLK1) is a non-canonical ligand of Notch signaling, which plays a pivotal role in vascular development and tumor angiogenesis. This study aimed to elucidate the function and mechanism of DLK1 in angiogenesis. METHODS AND RESULTS: By using in situ hybridization and immunohistochemical studies, expression analysis revealed a unique vascular tropism of DLK1 in vasculature of neuroblastoma and vascular tumors. Thus, it was hypothesized that DLK1 may be cleaved and then bound to endothelial cells, thereby regulating the endothelial function...
January 30, 2018: Angiogenesis
Xiaomin Chen, Tantan Gao, Qi Peng, Jie Zhang, Yunrong Chai, Fuping Song
In this study, a sporulation-specific gene (tentatively named cwlC) involved in mother cell lysis in Bacillus thuringiensis was characterized. The encoded CwlC protein consists of an N-terminal N-acetylmuramoyl-l-alanine amidase (MurNAc-LAA) domain and a C-terminal amidase02 domain. The recombinant histidine-tagged CwlC proteins purified from Escherichia coli were able to directly bind to and digest B. thuringiensis cell wall. The CwlC point mutations at the two conserved glutamic acid residues (Glu-24 and Glu-140) shown to be critical for the catalytic activity in homologous amidases resulted in a complete loss of cell wall lytic activity, suggesting that CwlC is an N-acetylmuramoyl-l-alanine amidase...
January 26, 2018: Applied and Environmental Microbiology
Kévin Moreau, Justine Surand, Aurélia Le Dantec, Christine Mosrin-Huaman, Alain Legrand, A Rachid Rahmouni
The alarming issue of antibiotic resistance expansion requires a continuous search for new and efficient antibacterial agents. Here we describe the design of new tools to screen for target-specific inhibitors of the bacterial Rho factor directly inside eukaryotic cells. Rho factor is a global regulator of gene expression which is essential to most bacteria, especially Gram-negative. Since Rho has no functional or structural homolog in eukaryotes, it constitutes a valuable and well known bacterial target as evidenced by its inhibition by the natural antibiotic, Bicyclomycin...
January 25, 2018: Journal of Antibiotics
Mario A Cerón-Romero, Esther Nwaka, Zuliat Owoade, Laura A Katz
The genome of P. falciparum, the causative agent of malaria in Africa, has been extensively studied since it was first fully sequenced in 2002. However, many open questions remain, including understanding the chromosomal context of molecular evolutionary changes (e.g. relationship between chromosome map and phylogenetic conservation, patterns of gene duplication, and patterns of selection). Here we present PhyloChromoMap, a method that generates a phylogenomic map of chromosomes from a custom-built bioinformatics pipeline...
January 22, 2018: Genome Biology and Evolution
Marion Eryilmaz, Eberhard Schmitt, Matthias Krufczik, Franziska Theda, Jin-Ho Lee, Christoph Cremer, Felix Bestvater, Wladimir Schaufler, Michael Hausmann, Georg Hildenbrand
In radiation biophysics, it is a subject of nowadays research to investigate DNA strand break repair in detail after damage induction by ionizing radiation. It is a subject of debate as to what makes up the cell's decision to use a certain repair pathway and how the repair machinery recruited in repair foci is spatially and temporarily organized. Single-molecule localization microscopy (SMLM) allows super-resolution analysis by precise localization of single fluorescent molecule tags, resulting in nuclear structure analysis with a spatial resolution in the 10 nm regime...
January 22, 2018: Cancers
Thi-Mong Diep Nguyen, Laura Filliatreau, Danièle Klett, Yves Combarnous
We have compared various Luteinizing Hormone (LH) and Choriogonadotropin (CG) preparations from non-human and human species in their ability to synergize with 10µM forskolin (FSK) for cyclic AMP intracellular accumulation, in MLTC cells. LH from rat pituitary as well as various isoforms of pituitary ovine, bovine, porcine, equine and human LHs and equine and human CG were studied. In addition, recombinant human LH and CG were also compared with the natural human and non-human hormones. Sub-stimulating concentrations of all LHs and CGs (2-100pM) were found to stimulate cyclic AMP accumulation in MLTC cells in the presence of an also non-stimulating FSK concentration (10µM)...
January 17, 2018: General and Comparative Endocrinology
Margaux Olivier, Cyril Charbonnel, Simon Amiard, Charles I White, Maria E Gallego
Replicative erosion of telomeres is naturally compensated by telomerase and studies in yeast and vertebrates show that homologous recombination can compensate for the absence of telomerase. We show that RAD51 protein, which catalyzes the key strand-invasion step of homologous recombination, is localized at Arabidopsis telomeres in absence of telomerase. Blocking the strand-transfer activity of the RAD51 in telomerase mutant plants results in a strikingly earlier onset of developmental defects, accompanied by increased numbers of end-to-end chromosome fusions...
January 13, 2018: Nucleic Acids Research
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