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homologous dependent recombination

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https://www.readbyqxmd.com/read/28101376/atpase-activity-tightly-regulates-reca-nucleofilaments-to-promote-homologous-recombination
#1
Bailin Zhao, Dapeng Zhang, Chengmin Li, Zheng Yuan, Fangzhi Yu, Shangwei Zhong, Guibin Jiang, Yun-Gui Yang, X Chris Le, Michael Weinfeld, Ping Zhu, Hailin Wang
Homologous recombination (HR), catalyzed in an evolutionarily conserved manner by active RecA/Rad51 nucleofilaments, maintains genomic integrity and promotes biological evolution and diversity. The structures of RecA/Rad51 nucleofilaments provide information critical for the entire HR process. By exploiting a unique capillary electrophoresis-laser-induced fluorescence polarization assay, we have discovered an active form of RecA nucleofilament, stimulated by ATP hydrolysis, that contains mainly unbound nucleotide sites...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28100589/meiotic-consequences-of-genetic-divergence-across-the-murine-pseudoautosomal-region
#2
Beth L Dumont
The production of haploid gametes during meiosis is dependent on the homology-driven processes of pairing, synapsis, and recombination. On the mammalian heterogametic sex chromosomes, these key meiotic activities are confined to the pseudoautosomal region (PAR), a short region of near-perfect sequence homology between the X and Y chromosomes. Despite its established importance for meiosis, the PAR is rapidly evolving, raising the question of how proper X/Y segregation is buffered against the accumulation of homology-disrupting mutations...
January 18, 2017: Genetics
https://www.readbyqxmd.com/read/28096179/dbf4-dependent-kinase-and-the-rtt107-scaffold-promote-mus81-mms4-resolvase-activation-during-mitosis
#3
Lissa N Princz, Philipp Wild, Julia Bittmann, F Javier Aguado, Miguel G Blanco, Joao Matos, Boris Pfander
DNA repair by homologous recombination is under stringent cell cycle control. This includes the last step of the reaction, disentanglement of DNA joint molecules (JMs). Previous work has established that JM resolving nucleases are activated specifically at the onset of mitosis. In case of budding yeast Mus81-Mms4, this cell cycle stage-specific activation is known to depend on phosphorylation by CDK and Cdc5 kinases. Here, we show that a third cell cycle kinase, Cdc7-Dbf4 (DDK), targets Mus81-Mms4 in conjunction with Cdc5-both kinases bind to as well as phosphorylate Mus81-Mms4 in an interdependent manner...
January 17, 2017: EMBO Journal
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/28069956/shuttling-along-dna-and-directed-processing-of-d-loops-by-recq-helicase-support-quality-control-of-homologous-recombination
#5
Gábor M Harami, Yeonee Seol, Junghoon In, Veronika Ferencziová, Máté Martina, Máté Gyimesi, Kata Sarlós, Zoltán J Kovács, Nikolett T Nagy, Yuze Sun, Tibor Vellai, Keir C Neuman, Mihály Kovács
Cells must continuously repair inevitable DNA damage while avoiding the deleterious consequences of imprecise repair. Distinction between legitimate and illegitimate repair processes is thought to be achieved in part through differential recognition and processing of specific noncanonical DNA structures, although the mechanistic basis of discrimination remains poorly defined. Here, we show that Escherichia coli RecQ, a central DNA recombination and repair enzyme, exhibits differential processing of DNA substrates based on their geometry and structure...
January 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28065599/homology-requirements-and-competition-between-gene-conversion-and-break-induced-replication-during-double-strand-break-repair
#6
Anuja Mehta, Annette Beach, James E Haber
Saccharomyces cerevisiae mating-type switching is initiated by a double-strand break (DSB) at MATa, leaving one cut end perfectly homologous to the HMLα donor, while the second end must be processed to remove a non-homologous tail before completing repair by gene conversion (GC). When homology at the matched end is ≤150 bp, efficient repair depends on the recombination enhancer, which tethers HMLα near the DSB. Thus, homology shorter than an apparent minimum efficient processing segment can be rescued by tethering the donor near the break...
December 22, 2016: Molecular Cell
https://www.readbyqxmd.com/read/28059164/pyruvic-oxime-dioxygenase-from-heterotrophic-nitrifier-alcaligenes-faecalis-is-a-nonheme-fe-ii-dependent-enzyme-homologous-to-class-ii-aldolase
#7
Shuhei Tsujino, Chisato Uematsu, Hideo Dohra, Taketomo Fujiwara
Pyruvic oxime dioxygenase (POD), a key enzyme in heterotrophic nitrification, was purified from Alcaligenes faecalis, and the molecular and catalytic characteristics were reexamined. POD was purified as the homotetramer of the subunit whose molecular weight was 30,000. The deduced amino acid sequence of POD was homologous with a class II aldolase that has been regarded as the Zn((II))-dependent enzyme catalyzing aldol reactions. The recombinant protein showed weak POD activity, and was activated by reconstitution with Fe((II))...
January 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28059076/structure-of-the-cohesin-loader-scc2
#8
William C H Chao, Yasuto Murayama, Sofía Muñoz, Andrew W Jones, Benjamin O Wade, Andrew G Purkiss, Xiao-Wen Hu, Aaron Borg, Ambrosius P Snijders, Frank Uhlmann, Martin R Singleton
The functions of cohesin are central to genome integrity, chromosome organization and transcription regulation through its prevention of premature sister-chromatid separation and the formation of DNA loops. The loading of cohesin onto chromatin depends on the Scc2-Scc4 complex; however, little is known about how it stimulates the cohesion-loading activity. Here we determine the large 'hook' structure of Scc2 responsible for catalysing cohesin loading. We identify key Scc2 surfaces that are crucial for cohesin loading in vivo...
January 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28053956/aberrant-dna-double-strand-break-repair-threads-in-breast-carcinoma-orchestrating-genomic-insult-survival
#9
REVIEW
Azad Kumar, Shruti Purohit, Nilesh Kumar Sharma
Breast carcinoma is a heterogeneous disease that has exhibited rapid resistance to treatment in the last decade. Depending genotype and phenotype of breast cancer, there are discernible differences in DNA repair protein responses including DNA double strand break repair. It is a fact that different molecular sub-types of breast carcinoma activate these dedicated protein pathways in a distinct manner. The DNA double-strand damage repair machinery is manipulated by breast carcinoma to selectively repair the damage or insults inflicted by the genotoxic effects of chemotherapy or radiation therapy...
December 2016: Journal of Cancer Prevention
https://www.readbyqxmd.com/read/28049850/resolution-of-single-and-double-holliday-junction-recombination-intermediates-by-gen1
#10
Rajvee Shah Punatar, Maria Jose Martin, Haley D M Wyatt, Ying Wai Chan, Stephen C West
Genetic recombination provides an important mechanism for the repair of DNA double-strand breaks. Homologous pairing and strand exchange lead to the formation of DNA intermediates, in which sister chromatids or homologous chromosomes are covalently linked by four-way Holliday junctions (HJs). Depending on the type of recombination reaction that takes place, intermediates may have single or double HJs, and their resolution is essential for proper chromosome segregation. In mitotic cells, double HJs are primarily dissolved by the BLM helicase-TopoisomeraseIIIα-RMI1-RMI2 (BTR) complex, whereas single HJs (and double HJs that have escaped the attention of BTR) are resolved by structure-selective endonucleases known as HJ resolvases...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28031483/speedy-a-cdk2-binding-mediates-initial-telomere-nuclear-envelope-attachment-during-meiotic-prophase-i-independent-of-cdk2-activation
#11
Zhaowei Tu, Mustafa Bilal Bayazit, Hongbin Liu, Jingjing Zhang, Kiran Busayavalasa, Sanjiv Risal, Jingchen Shao, Ande Satyanarayana, Vincenzo Coppola, Lino Tessarollo, Meenakshi Singh, Chunwei Zheng, Chunsheng Han, Zijiang Chen, Philipp Kaldis, Jan-Åke Gustafsson, Kui Liu
Telomere attachment to the nuclear envelope (NE) is a prerequisite for chromosome movement during meiotic prophase I that is required for pairing of homologous chromosomes, synapsis, and homologous recombination. Here we show that Speedy A, a noncanonical activator of cyclin-dependent kinases (Cdks), is specifically localized to telomeres in prophase I male and female germ cells in mice, and plays an essential role in the telomere-NE attachment. Deletion of Spdya in mice disrupts telomere-NE attachment, and this impairs homologous pairing and synapsis and leads to zygotene arrest in male and female germ cells...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28011904/multifunctional-roles-of-saccharomyces-cerevisiae-srs2-protein-in-replication-recombination-and-repair
#12
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
#13
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
https://www.readbyqxmd.com/read/28009280/three-dimensional-architecture-of-the-human-brca1-a-histone-deubiquitinase-core-complex
#14
Otto J P Kyrieleis, Pauline B McIntosh, Sarah R Webb, Lesley J Calder, Janette Lloyd, Nisha A Patel, Stephen R Martin, Carol V Robinson, Peter B Rosenthal, Stephen J Smerdon
BRCA1 is a tumor suppressor found to be mutated in hereditary breast and ovarian cancer and plays key roles in the maintenance of genomic stability by homologous recombination repair. It is recruited to damaged chromatin as a component of the BRCA1-A deubiquitinase, which cleaves K63-linked ubiquitin chains attached to histone H2A and H2AX. BRCA1-A contributes to checkpoint regulation, repair pathway choice, and HR repair efficiency through molecular mechanisms that remain largely obscure. The structure of an active core complex comprising two Abraxas/BRCC36/BRCC45/MERIT40 tetramers determined by negative-stain electron microscopy (EM) reveals a distorted V-shape architecture in which a dimer of Abraxas/BRCC36 heterodimers sits at the base, with BRCC45/Merit40 pairs occupying each arm...
December 20, 2016: Cell Reports
https://www.readbyqxmd.com/read/28007892/feeding-related-traits-are-affected-by-dosage-of-the-foraging-gene-in-drosophila-melanogaster
#15
Aaron M Allen, Ina Anreiter, Megan C Neville, Marla B Sokolowski
Nutrient acquisition and energy storage are critical parts of achieving metabolic homeostasis. The foraging gene in Drosophila melanogaster has previously been implicated in multiple feeding-related and metabolic traits. Before foraging's functions can be further dissected, we need a precise genetic null mutant to definitively map its amorphic phenotypes. We used homologous recombination to precisely delete foraging, generating the for(0) null allele, and used recombineering to re-integrate a full copy of the gene, generating the {for(BAC)} rescue allele...
December 22, 2016: Genetics
https://www.readbyqxmd.com/read/27993973/anaplasma-marginale-outer-membrane-protein-a-is-an-adhesin-that-recognizes-sialylated-and-fucosylated-glycans-and-functionally-depends-on-an-essential-binding-domain
#16
Kathryn S Hebert, David Seidman, Aminat T Oki, Jerilyn Izac, Sarvani Emani, Lee D Oliver, Daniel P Miller, Brittney K Tegels, Reiji Kannagi, Richard T Marconi, Jason A Carlyon
Anaplasma marginale causes bovine anaplasmosis, a debilitating and potentially fatal tick-borne infection of cattle. Because A. marginale is an obligate intracellular organism, its adhesins that mediate entry into host cells are essential for survival. Here, we demonstrate that A. marginale outer membrane protein A (AmOmpA; AM854) contributes to the invasion of mammalian and tick host cells. AmOmpA exhibits predicted structural homology to OmpA of A. phagocytophilum (ApOmpA), an adhesin that uses key lysine and glycine residues to interact with α2,3-sialylated and α1,3-fucosylated glycan receptors, including 6-sulfo-sialyl Lewis x...
December 19, 2016: Infection and Immunity
https://www.readbyqxmd.com/read/27989837/prophenoloxidase-activation-and-antimicrobial-peptide-expression-induced-by-the-recombinant-microbe-binding-protein-of-manduca-sexta
#17
Yang Wang, Haobo Jiang
Manduca sexta microbe binding protein (MBP) is a member of the β-1,3-glucanase-related protein superfamily that includes Gram-negative bacteria-binding proteins (GNBPs), β-1,3-glucan recognition proteins (βGRPs), and β-1,3-glucanases. Our previous and current studies showed that the purified MBP from baculovirus-infected insect cells had stimulated prophenoloxidase (proPO) activation in the hemolymph of naïve and immune challenged larvae and that supplementation of the exogenous MBP and peptidoglycans (PGs) had caused synergistic increases in PO activity...
October 28, 2016: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27989139/unpredicted-downregulation-of-rad51-suggests-genome-instability-induced-by-tetrachlorobenzoquinone
#18
Xiufang Song, Qiong Shi, Zixuan Liu, Yawen Wang, Yuxin Wang, Erqun Song, Yang Song
We previously demonstrated that halogenated quinone induces DNA double strand breaks (DSBs) in a ROS-dependent manner, which coordinates with downstream repair cascade including nonhomologous end joining, base excision repair, and nucleotide excision repair. However, these error-prone processes may cause the potential risk of genome instability, and current has no information on how faithful repair route, such as homologous recombination (HR), was affected. RAD51 is a key protein in the HR pathway of DSBs repair...
December 19, 2016: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/27984745/rad52-facilitates-mitotic-dna-synthesis-following-replication-stress
#19
Rahul Bhowmick, Sheroy Minocherhomji, Ian D Hickson
Homologous recombination (HR) is necessary to counteract DNA replication stress. Common fragile site (CFS) loci are particularly sensitive to replication stress and undergo pathological rearrangements in tumors. At these loci, replication stress frequently activates DNA repair synthesis in mitosis. This mitotic DNA synthesis, termed MiDAS, requires the MUS81-EME1 endonuclease and a non-catalytic subunit of the Pol-delta complex, POLD3. Here, we examine the contribution of HR factors in promoting MiDAS in human cells...
December 15, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27974736/hed1-promotes-meiotic-crossover-formation-in-saccharomyces-cerevisiae
#20
Yoon-Ju Kong, Jeong-Hwan Joo, Keun Pil Kim, Soogil Hong
Homologous recombination (HR) occurs between homologous chromosomes and is significantly involved in programmed double-strand breaks (DSB) repair. Activation of two recombinases, Rad51 and Dmc1, is essential for an inter-homolog bias during meiosis. Rad51 participates in both mitotic and meiotic recombination, and its strand exchange activity is regulated by an inhibitory factor during meiosis. Thus, activities of Rad51 and Dmc1 are coordinated to promote homolog bias. It has been reported that Hed1, a meiosis-specific protein in budding yeast, regulates Rad51-dependent recombination activity...
December 14, 2016: Journal of Microbiology and Biotechnology
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