Implications of Metastable Nicks and Nicked Holliday Junctions in Processing Joint Molecules in Mitosis and Meiosis
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
An RNA Holliday Junction? Structural and Dynamic Considerations of the Bacteriophage T4 Gene 60 Interruption
J. Mol. Biol. (1990) 213, 199-201 COMMUNICATIONS An RNA Holliday Junction? Structural and Dynamic Considerations of the Bacteriophage T4 Gene 60 Interruption Donald H. Burke-Agiiero and John E. Hearst Department of Chemistry University of California, Laboratory of Chemical Biodynamics Lawrence Berkeley Laboratory, Berkeley, CA 94720, U.S.A. (Received 20 June 1988; accepted 20 November 1989) A novel interrupted gene motif has been reported in which a 50-nucleotide insertion into bacteriophage T4 gene 60 appears to be present in the message at the time of translation, yet it is not translated. We present here a dynamic model for how translation may be occurring in the neighborhood of the interruption. The model involves formation of an RNA structure with similarities to a Holliday junction, followed by migration of the branch point in a strand exchange between message and interruption. The advantage of this model over previous ones is that at no time is a new tRNA required to pair with a discontinuous template. Huang et al. (1988) have reported a novel gene tion; the order of events is not important to this interruption motif in gene 60 of bacteriophage T4, model. More extensive branch migration is hindered in which a 50-nucleotide intervening segment is by the lack of sequence homology between the neither removed nor translated. The sequence of the message and the dumbbell outside these five bases. interruption suggests that it can be folded to bring When tRNA G~y moves into the P site, the template the translated codons on either side of the inter- 3' to Gly46 will now be in position to receive the ruption into close proximity (Fig. -
The Escherichia Coli Ruvb Branch Migration Protein Forms Double
Proc. Natl. Acad. Sci. USA Vol. 91, pp. 7618-7622, August 1994 Biophysics The Escherichia coli RuvB branch migration protein forms double hexameric rings around DNA (DNA helicase/three-dmensonal reconsuctlon/dectron microscopy) ANDRZEJ STASIAK*, IRINA R. TSANEVAt, STEPHEN C. WESTt, CATHERINE J. B. BENSON*, XIONG Yul, AND EDWARD H. EGELMANO§ *Laboratory of Ultrastructural Analysis, University of Lausanne, CH-1015 Lausanne, Switzerland; tClare Hall Laboratories, Imperial Cancer Research Fund, South Mimms, Herts. EN6 3LD, United Kingdom; and *Department of Cell Biology and Neuroanatomy, University of Minnesota Medical School, Minneapolis, MN 55455 Communicated by Philip C. Hanawalt, April 22, 1994 (receivedfor review February 25, 1994) ABSTRACT The RuvB protein is induced in Escherichia MATERIALS AND METHODS coft as part of the SOS response to DNA damage. It is required for genetic recombination and the postreplication repair of Preparation of RuvB-DNA Complexes. The RuvB protein DNA. In vitro, the RuvB protein promotes the branch migra- was purified as described (18) and incubated (at 150 pg/ml) tion of Holliday junctions and has a DNA helicase activt in for 5 min at 370C with relaxed 4X174 DNA (10 pLg/ml), 15 mM reactions that require ATP hydrolysis. We have used electron MgAc, and 1 mM adenosine [y-thio]triphosphate (ATP[y-S]) microscopy, image analysis, and three-dimensional reconstruc- in a 20 mM triethanolamine acetate buffer, pH 7.5. tion to show that the RuvB protein, in the presence of ATP, Eleron Miroscopy. The samples (either RuvB-ATP(y'SJ- forms a dodecamer on double-stranded DNA in which two DNA complexes or RuvB-ATP[(-S]) were stained with 2% stacked hexameric rings encircle the DNA and are oriented in uranyl acetate, and images were recorded under minimal-dose opposite directions with D6 symmetry. -
The Kinetics of Spontaneous DNA Branch Migration IGOR G
Proc. Nat!. Acad. Sci. USA Vol. 91, pp. 2021-2025, March 1994 Biochemistry The kinetics of spontaneous DNA branch migration IGOR G. PANYUTIN AND PEGGY HSIEH Genetics and Biochemistry Branch, National Institute of Diabetes and Kidney and Digestive Diseases, National Institutes of Health, Bethesda, MD 20892 Communicated by Howard A. Nash, November 1, 1993 ABSTRACT An important step in genetic recombination is In addition to knowing the inherent rate of branch migra- DNA branch migration, the movement ofthe Hollidayjunction tion, it is also critical to know whether spontaneous branch or exchange point between two homologous duplex DNAs. We migration can traverse sequence heterology such as mis- have determined kinetic parameters of spontaneous branch matches, insertions, and deletions since homologous recom- migration as a function of temperature and ionic conditions. bination usually involves the exchange of DNA strands The branch migration substrates consist of two homologous between two similar but not identical duplexes. We recently duplex DNAs each having two single-strand tails at one end that observed that a single base mismatch was sufficient to slow are complementary to the corresponding singe-strand tails of the overall rate of branch migration (5). Moreover, this the other duplex. Upon rapid annealing of the two duplex attenuation by sequence heterology was more pronounced in DNAs, a four-stranded intermediate is formed that has a magnesium than in sodium, suggesting that branch migration Holliday junction at one end ofthe duplexes. Branch migration is influenced by metal ions. to the end of the results in strand To clarify questions concerning the intrinsic rate ofbranch opposite duplexes complete migration, we have developed an improved assay for branch exchange and formation of two duplex products. -
Helicase Mechanisms During Homologous Recombination in Saccharomyces Cerevisiae
BB48CH11_Greene ARjats.cls April 18, 2019 12:24 Annual Review of Biophysics Helicase Mechanisms During Homologous Recombination in Saccharomyces cerevisiae J. Brooks Crickard and Eric C. Greene Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; email: [email protected], [email protected] Annu. Rev. Biophys. 2019. 48:255–73 Keywords First published as a Review in Advance on homologous recombination, helicase, Srs2, Sgs1, Rad54 March 11, 2019 Access provided by 68.175.70.229 on 06/02/20. For personal use only. The Annual Review of Biophysics is online at Abstract Annu. Rev. Biophys. 2019.48:255-273. Downloaded from www.annualreviews.org biophys.annualreviews.org Helicases are enzymes that move, manage, and manipulate nucleic acids. https://doi.org/10.1146/annurev-biophys-052118- They can be subdivided into six super families and are required for all aspects 115418 of nucleic acid metabolism. In general, all helicases function by converting Copyright © 2019 by Annual Reviews. the chemical energy stored in the bond between the gamma and beta phos- All rights reserved phates of adenosine triphosphate into mechanical work, which results in the unidirectional movement of the helicase protein along one strand of a nu- cleic acid. The results of this translocation activity can range from separation of strands within duplex nucleic acids to the physical remodeling or removal of nucleoprotein complexes. In this review, we focus on describing key heli- cases from the model organism Saccharomyces cerevisiae that contribute to the regulation of homologous recombination, which is an essential DNA repair pathway for fxing damaged chromosomes. -
The Role of Blm Helicase in Homologous Recombination, Gene Conversion Tract Length, and Recombination Between Diverged Sequences in Drosophila Melanogaster
| INVESTIGATION The Role of Blm Helicase in Homologous Recombination, Gene Conversion Tract Length, and Recombination Between Diverged Sequences in Drosophila melanogaster Henry A. Ertl, Daniel P. Russo, Noori Srivastava, Joseph T. Brooks, Thu N. Dao, and Jeannine R. LaRocque1 Department of Human Science, Georgetown University Medical Center, Washington, DC 20057 ABSTRACT DNA double-strand breaks (DSBs) are a particularly deleterious class of DNA damage that threatens genome integrity. DSBs are repaired by three pathways: nonhomologous-end joining (NHEJ), homologous recombination (HR), and single-strand annealing (SSA). Drosophila melanogaster Blm (DmBlm) is the ortholog of Saccharomyces cerevisiae SGS1 and human BLM, and has been shown to suppress crossovers in mitotic cells and repair mitotic DNA gaps via HR. To further elucidate the role of DmBlm in repair of a simple DSB, and in particular recombination mechanisms, we utilized the Direct Repeat of white (DR-white) and Direct Repeat of white with mutations (DR-white.mu) repair assays in multiple mutant allele backgrounds. DmBlm null and helicase-dead mutants both demonstrated a decrease in repair by noncrossover HR, and a concurrent increase in non-HR events, possibly including SSA, crossovers, deletions, and NHEJ, although detectable processing of the ends was not significantly impacted. Interestingly, gene conversion tract lengths of HR repair events were substantially shorter in DmBlm null but not helicase-dead mutants, compared to heterozygote controls. Using DR-white.mu,we found that, in contrast to Sgs1, DmBlm is not required for suppression of recombination between diverged sequences. Taken together, our data suggest that DmBlm helicase function plays a role in HR, and the steps that contribute to determining gene conversion tract length are helicase-independent. -
Holliday Junction Resolvases
Downloaded from http://cshperspectives.cshlp.org/ on September 23, 2021 - Published by Cold Spring Harbor Laboratory Press Holliday Junction Resolvases Haley D.M. Wyatt and Stephen C. West London Research Institute, Cancer Research UK, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, United Kingdom Correspondence: [email protected] Four-way DNA intermediates, called Holliday junctions (HJs), can form during meiotic and mitotic recombination, and their removal is crucial for chromosome segregation. A group of ubiquitous and highly specialized structure-selective endonucleases catalyze the cleavage of HJs into two disconnected DNA duplexes in a reaction called HJ resolution. These enzymes, called HJ resolvases, have been identified in bacteria and their bacteriophages, archaea, and eukaryotes. In this review, we discuss fundamental aspects of the HJ structure and their interaction with junction-resolving enzymes. This is followed by a brief discussion of the eubacterial RuvABC enzymes, which provide the paradigm for HJ resolvases in other organisms. Finally, we review the biochemical and structural properties of some well-char- acterized resolvases from archaea, bacteriophage, and eukaryotes. omologous recombination (HR) is an es- homologous strand as a template for DNA syn- Hsential process that promotes genetic di- thesis. Recombination then proceeds in one of versity during meiosis (see Lam and Keeney several different ways, some of which involve 2014; Zickler and Kleckner 2014). However, in second-end capture, such that the other resect- somatic cells, HR plays a key role in conserv- ed 30 end anneals to the displaced strand of the ing genetic information by facilitating DNA re- D-loop (Szostak et al. -
A Mutation in the Putative MLH3 Endonuclease Domain Confers a Defect in Both Mismatch Repair and Meiosis in Saccharomyces Cerevisiae
Copyright Ó 2008 by the Genetics Society of America DOI: 10.1534/genetics.108.086645 A Mutation in the Putative MLH3 Endonuclease Domain Confers a Defect in Both Mismatch Repair and Meiosis in Saccharomyces cerevisiae K. T. Nishant, Aaron J. Plys and Eric Alani1 Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853-2703 Manuscript received January 2, 2008 Accepted for publication March 20, 2008 ABSTRACT Interference-dependent crossing over in yeast and mammalian meioses involves the mismatch repair protein homologs MSH4-MSH5 and MLH1-MLH3. The MLH3 protein contains a highly conserved metal- binding motif DQHA(X)2E(X)4E that is found in a subset of MLH proteins predicted to have endonuclease activities (Kadyrov et al. 2006). Mutations within this motif in human PMS2 and Saccharomyces cerevisiae PMS1 disrupted the endonuclease and mismatch repair activities of MLH1-PMS2 and MLH1-PMS1, re- spectively (Kadyrov et al. 2006, 2007; Erdeniz et al. 2007). As a first step in determining whether such an activity is required during meiosis, we made mutations in the MLH3 putative endonuclease domain motif (-D523N, -E529K) and found that single and double mutations conferred mlh3-null-like defects with respect to meiotic spore viability and crossing over. Yeast two-hybrid and chromatography analyses showed that the interaction between MLH1 and mlh3-D523N was maintained, suggesting that the mlh3-D523N mutation did not disrupt the stability of MLH3. The mlh3-D523N mutant also displayed a mutator phenotype in vegetative growth that was similar to mlh3D. Overexpression of this allele conferred a dominant-negative phenotype with respect to mismatch repair. -
A Genome-Wide Screen for Genes Affecting Spontaneous Direct-Repeat Recombination In
bioRxiv preprint doi: https://doi.org/10.1101/2020.02.11.943795; this version posted February 11, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 A genome-wide screen for genes affecting spontaneous direct-repeat recombination in 2 Saccharomyces cerevisiae 3 4 5 Daniele Novarina*, Ridhdhi Desai†, Jessica A. Vaisica†, Jiongwen Ou†, Mohammed Bellaoui†,1, 6 Grant W. Brown†,2 and Michael Chang*,3 7 8 *European Research Institute for the Biology of Ageing, University of Groningen, University 9 Medical Center Groningen, 9713 AV Groningen, the Netherlands 10 †Department of Biochemistry and Donnelly Centre, University of Toronto, Toronto, ON M5S 11 3E1, Canada 12 13 1Current address: Genetics Unit, Faculty of Medicine and Pharmacy, University Mohammed 14 Premier, Oujda, Morocco 15 16 2Co-corresponding author: Department of Biochemistry and Donnelly Centre, University of 17 Toronto, 160 College Street, Toronto, ON M5S 3E1 Canada. E-mail: [email protected] 18 3Co-corresponding author: European Research Institute for the Biology of Ageing, University of 19 Groningen, University Medical Center Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, 20 the Netherlands. E-mail: [email protected] 21 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.02.11.943795; this version posted February 11, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. -
Insights Into Holliday Junction Resolution and Chromosome Segregation in Yeast
September 17, 2012 SCIENCE SPOTLIGHT Insights into Holliday Junction Resolution and Chromosome Segregation in Yeast September 17, 2012 ME Arnegard Homologous DNA recombination is the highly conserved process by which similar or identical nucleotide sequences are exchanged between two DNA molecules. In all eukaryotes – from yeast to humans – this kind of genetic recombination serves two critical functions during meiosis, the class of cell division that leads to the formation of gametes such as sperm and eggs in the case of humans, or spores in yeast: Homologous recombination promotes the genetic diversity of gametes by allowing crossing-over between homologous chromosomes, and it is also critical to accurate chromosome segregation during meiosis. Anomalies in recombination often result in the complete loss of chromosomes during meiosis, or in chromosomal rearrangements such as deletions or translocations, which in turn can lead to birth defects or cancer. All current models for crossing-over involve two key intermediate structures: DNA double strand breaks (DSBs) and Holliday junctions (HJs). DSBs are the initiating events in crossing-over that are caused by Rec12 in fission yeast, whereas HJs are the crossed-strand structures by which DNA molecules from two homologous chromosomes become intertwined (see figure). At the Fred Hutchinson Cancer Research Center, the laboratory of Dr. Gerald Smith (Basic Sciences Division) has made many advances toward understanding a complex pathway composed of dozens of proteins that promote homologous recombination in fission yeast (Schizosaccharomyces pombe) by moving or pairing chromosomes, or forming or repairing DSBs. In a previous study, for example, Cromie et al. (2006) provided strong evidence that HJs in fission yeast are 'resolved' (i.e., precisely cut and reconnected into two independent helices) solely by the endonucleolytic activity of the partner proteins Mus81 and Eme1. -
Fanconi Anemia, Bloom Syndrome and Breast Cancer
A multiprotein complex in DNA damage response network of Fanconi anemia, Bloom syndrome and Breast cancer Weidong Wang Lab of Genetics, NIA A Multi-protein Complex Connects Two Genomic Instability Diseases: Bloom Syndrome and Fanconi Anemia Bloom Syndrome . Genomic Instability: -sister-chromatid exchange . Cancer predisposition . Mutation in BLM, a RecQ DNA Helicase . BLM participates in: HR-dependent DSB repair Recovery of stalled replication forks . BLM works with Topo IIIa and RMI to Suppress crossover recombination Courtesy of Dr. Ian Hickson A Multi-protein Complex Connects Two Genomic Instability Diseases: Bloom Syndrome and Fanconi Anemia P I l o r t n o BLM IP kDa C HeLa BLAP 250 Nuclear Extract 200- BLM* FANCA* 116- TOPO IIIα* 97- BLAP 100 MLH1* BLM IP BLAP 75 * 66- RPA 70 IgG H 45- * 30- RPA32 IgG L 20- * 12- RPA14 Meetei et al. MCB 2003 A Multi-protein Complex Connects Two Genomic Instability Diseases: Bloom Syndrome and Fanconi Anemia P I A C N A F BLM IP HeLa FANCM= FAAP 250 BLAP 250 Nuclear Extract BLM* BLM* * FANCA* FANCA TOPO IIIα* TOPO IIIα* FAAP 100 BLAP 100 FANCB= FAAP 95 MLH1 FANCA IP BLM IP BLAP 75 BLAP 75 RPA70*/FANCG* RPA 70* FANCC*/FANCE* IgG H FANCL= FAAP 43 FANCF* RPA32* IgG L Meetei et al. MCB 2003 Meetei et al. Nat Genet. 2003, 2004, 2005 BRAFT-a Multisubunit Machine that Maintains Genome Stability and is defective in Fanconi anemia and Bloom syndrome BRAFT Super-complex Fanconi Anemia Bloom Syndrome Core Complex Complex 12 polypeptides 7 polypeptides FANCA BLM Helicase (HJ, fork, D-loop), fork FANCC regression, dHJ dissolution Topo IIIα Topoisomerase, FANCE dHJ dissolution FANCF BLAP75 RMI1 FANCG Stimulates dHJ dissolution. -
Recombinational DNA Repair in Bacteria: Postreplication
Recombinational DNA Secondary article Repair in Bacteria: Article Contents . Introduction Postreplication . What Leads to Recombinational DNA Repair? . Proteins Involved in Recombinational DNA Repair Kevin P Rice, University of Wisconsin-Madison, Madison, Wisconsin, USA . Pathways . Replication Restart Associated with the SOS Response Michael M Cox, University of Wisconsin-Madison, Madison, Wisconsin, USA . Summary Recombinational DNA repair represents the primary function for homologous DNA recombination in bacteria. Most of this repair occurs at replication forks that are stalled at sites of DNA damage. Introduction fork (including DNA polymerase III and the DnaG and Deoxyribonucleic acid (DNA) damage is a common DnaB proteins) processes in each direction from that occurrence in all cells. A bacterial cell growing in an origin. The forks eventually meet, yielding two identical aerobic environment will suffer 3000–5000 DNA lesions copies ofthe bacterium’s genetic material. per cell per generation (most ofthem oxidative in origin). Recombinational DNA repair ensues whenever a Most of this damage is faithfully repaired by specialized replication fork is halted by DNA damage prior to normal DNA repair systems; however, replication forks will replication termination. There are at least two major types occasionally encounter unrepaired DNA lesions. Because ofdamage and corresponding pathways fortheir repair DNA polymerase is usually unable to bypass DNA (Figure 1). Ifthe forkencounters a DNA strand break, a damage, the complex breaks down in what is best described double-strand break that separates one branch ofthe fork as an enzymatic train wreck. Under normal cellular growth from the rest results. Alternatively, the fork might conditions, nearly every bacterial replication fork will encounter an unrepaired DNA lesion, leaving the lesion suffer this fate. -
Assembly of the Escherichia Coli Ruvabc Resolvasome Directs the Orientation of Holliday Junction Resolution
Downloaded from genesdev.cshlp.org on September 24, 2021 - Published by Cold Spring Harbor Laboratory Press Assembly of the Escherichia coli RuvABC resolvasome directs the orientation of Holliday junction resolution Alain J. van Gool,3 Nasser M.A. Hajibagheri,1 Andrzej Stasiak,2 and Stephen C. West4 Genetic Recombination Laboratory, Imperial Cancer Research Fund (ICRF) South Mimms, Herts EN6 3LD, UK; 1Electron Microscopy Unit, Imperial Cancer Research Fund, London WC2A 3PX, UK; 2Laboratoire d’Analyse Ultrastructurale, Universite´de Lausanne, Lausanne, Switzerland Genetic recombination can lead to the formation of intermediates in which DNA molecules are linked by Holliday junctions. Movement of a junction along DNA, by a process known as branch migration, leads to heteroduplex formation, whereas resolution of a junction completes the recombination process. Holliday junctions can be resolved in either of two ways, yielding products in which there has, or has not, been an exchange of flanking markers. The ratio of these products is thought to be determined by the frequency with which the two isomeric forms (conformers) of the Holliday junction are cleaved. Recent studies with enzymes that process Holliday junctions in Escherichia coli, the RuvABC proteins, however, indicate that protein binding causes the junction to adopt an open square-planar configuration. Within such a structure, DNA isomerization can have little role in determining the orientation of resolution. To determine the role that junction-specific protein assembly has in determining resolution bias, a defined in vitro system was developed in which we were able to direct the assembly of the RuvABC resolvasome. We found that the bias toward resolution in one orientation or the other was determined simply by the way in which the Ruv proteins were positioned on the junction.