DNA Damage Response Pathways in the Nematode C. Elegans
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Meiotic Development in Caenorhabditis Elegans
Chapter 6 Meiotic Development in Caenorhabditis elegans Doris Y. Lui and Monica P. Colaiácovo Abstract Caenorhabditis elegans has become a powerful experimental organism with which to study meiotic processes that promote the accurate segregation of chromosomes during the generation of haploid gametes. Haploid reproductive cells are produced through one round of chromosome replication followed by two successive cell divisions. Characteristic meiotic chromosome structure and dynam- ics are largely conserved in C. elegans . Chromosomes adopt a meiosis-speci fi c structure by loading cohesin proteins, assembling axial elements, and acquiring chromatin marks. Homologous chromosomes pair and form physical connections though synapsis and recombination. Synaptonemal complex and crossover forma- tion allow for the homologs to stably associate prior to remodeling that facilitates their segregation. This chapter will cover conserved meiotic processes as well as highlight aspects of meiosis that are unique to C. elegans . Keywords Meiosis • Pairing • Recombination • Synapsis • Cohesion • Germline • C. elegans 6.1 Introduction Meiosis is a specialized cell division process by which sexually reproducing diploid organisms, including humans, produce haploid gametes (i.e., eggs and sperm) to be used for fertilization. This halving in the number of chromosomes is accomplished by following one round of DNA replication with two consecu- tive rounds of chromosome segregation (meiosis I and meiosis II). Whereas D. Y. Lui • M. P. Colaiácovo (*) Department of Genetics , Harvard Medical School , Boston , MA 02115 , USA e-mail: [email protected] T. Schedl (ed.), Germ Cell Development in C. elegans, Advances in Experimental 133 Medicine and Biology 757, DOI 10.1007/978-1-4614-4015-4_6, © Springer Science+Business Media New York 2013 134 D.Y. -
Research in Biology Using Computation Doi
Journal of Bioinformatics and Genomics 2 (7) 2018 RESEARCH IN BIOLOGY USING COMPUTATION DOI: https://doi.org/10.18454/jbg.2018.2.7.1 Grishaeva T.M.* Department of Cytogenetics, Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russian Federation * Correspodning author (grishaeva[at]vigg.ru) Received: 18.03.2018; Accepted: 05.04.2018; Published: 22.05.2018 COMPARATIVE CONSERVATION OF MEIOTIC PROTEINS IN DIFFERENT PHYLOGENETIC LINES OF EUKARYOTES Research article Abstract Motivation: Meiosis — a two-stage process of sex cell division — is served by several hundreds of proteins. A part of them went to eukaryotes from prokaryotes, others appeared in first eukaryotes, and some proteins appeared de novo in multicellular eukaryotes. We compared the conservation of proteins involved in various processes occurring in meiosis. Results: The conservations of five meiotic enzymes (MLH1, MRE11, MSH4, BRCA1, BRCA2) and three silencing markers (histone H2AX, SUMO1, ATR) were compared using a set of bioinformatics methods. Orthologs of these proteins from the proteomes of model species were compared, representing different lines of development of eukaryotes. Among the enzymes, the most conserved is MLH1, which provide correction of mismatch bases, and the least conserved are BRCA1 and BRCA2 repair enzymes which are present only in vertebrates. Among silencing proteins, histone H2AX is the most conserved one, playing the central part in the regulation of the transcription, in the repair and replication of DNA. The small protein SUMO1, which is involved in many cellular processes, is less conserved. ATR kinase in different species is similar only in the C-terminal part of the molecule. -
The Role of Caspase-2 in Regulating Cell Fate
cells Review The Role of Caspase-2 in Regulating Cell Fate Vasanthy Vigneswara and Zubair Ahmed * Neuroscience and Ophthalmology, Institute of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, UK; [email protected] * Correspondence: [email protected] Received: 15 April 2020; Accepted: 12 May 2020; Published: 19 May 2020 Abstract: Caspase-2 is the most evolutionarily conserved member of the mammalian caspase family and has been implicated in both apoptotic and non-apoptotic signaling pathways, including tumor suppression, cell cycle regulation, and DNA repair. A myriad of signaling molecules is associated with the tight regulation of caspase-2 to mediate multiple cellular processes far beyond apoptotic cell death. This review provides a comprehensive overview of the literature pertaining to possible sophisticated molecular mechanisms underlying the multifaceted process of caspase-2 activation and to highlight its interplay between factors that promote or suppress apoptosis in a complicated regulatory network that determines the fate of a cell from its birth and throughout its life. Keywords: caspase-2; procaspase; apoptosis; splice variants; activation; intrinsic; extrinsic; neurons 1. Introduction Apoptosis, or programmed cell death (PCD), plays a pivotal role during embryonic development through to adulthood in multi-cellular organisms to eliminate excessive and potentially compromised cells under physiological conditions to maintain cellular homeostasis [1]. However, dysregulation of the apoptotic signaling pathway is implicated in a variety of pathological conditions. For example, excessive apoptosis can lead to neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease, whilst insufficient apoptosis results in cancer and autoimmune disorders [2,3]. Apoptosis is mediated by two well-known classical signaling pathways, namely the extrinsic or death receptor-dependent pathway and the intrinsic or mitochondria-dependent pathway. -
And Cis Lack of Involvement in in Ig Class Switch Recombination
Reassessment of the Role of Mut S Homolog 5 in Ig Class Switch Recombination Shows Lack of Involvement in cis- and trans -Switching This information is current as of September 26, 2021. Jeroen E. J. Guikema, Carol E. Schrader, Niek G. J. Leus, Anna Ucher, Erin K. Linehan, Uwe Werling, Winfried Edelmann and Janet Stavnezer J Immunol 2008; 181:8450-8459; ; doi: 10.4049/jimmunol.181.12.8450 Downloaded from http://www.jimmunol.org/content/181/12/8450 References This article cites 54 articles, 30 of which you can access for free at: http://www.jimmunol.org/ http://www.jimmunol.org/content/181/12/8450.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on September 26, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2008 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Reassessment of the Role of Mut S Homolog 5 in Ig Class Switch Recombination Shows Lack of Involvement in cis- and trans-Switching1 Jeroen E. -
VDAC1 Is Essential for Neurite Maintenance and the Inhibition Of
www.nature.com/scientificreports OPEN VDAC1 is essential for neurite maintenance and the inhibition of its oligomerization protects Received: 4 July 2019 Accepted: 4 September 2019 spinal cord from demyelination Published: xx xx xxxx and facilitates locomotor function recovery after spinal cord injury Vera Paschon1, Beatriz Cintra Morena1, Felipe Fernandes Correia1, Giovanna Rossi Beltrame1, Gustavo Bispo dos Santos2, Alexandre Fogaça Cristante2 & Alexandre Hiroaki Kihara 1 During the progression of the neurodegenerative process, mitochondria participates in several intercellular signaling pathways. Voltage-dependent anion-selective channel 1 (VDAC1) is a mitochondrial porin involved in the cellular metabolism and apoptosis intrinsic pathway in many neuropathological processes. In spinal cord injury (SCI), after the primary cell death, a secondary response that comprises the release of pro-infammatory molecules triggers apoptosis, infammation, and demyelination, often leading to the loss of motor functions. Here, we investigated the functional role of VDAC1 in the neurodegeneration triggered by SCI. We frst determined that in vitro targeted ablation of VDAC1 by specifc morpholino antisense nucleotides (MOs) clearly promotes neurite retraction, whereas a pharmacological blocker of VDAC1 oligomerization (4, 4′-diisothiocyanatostilbene-2, 2′-disulfonic acid, DIDS), does not cause this efect. We next determined that, after SCI, VDAC1 undergoes conformational changes, including oligomerization and N-terminal exposition, which are important steps in the triggering of apoptotic signaling. Considering this, we investigated the efects of DIDS in vivo application after SCI. Interestingly, blockade of VDAC1 oligomerization decreases the number of apoptotic cells without interfering in the neuroinfammatory response. DIDS attenuates the massive oligodendrocyte cell death, subserving undisputable motor function recovery. Taken together, our results suggest that the prevention of VDAC1 oligomerization might be benefcial for the clinical treatment of SCI. -
The Choice in Meiosis – Defining the Factors That Influence Crossover Or Non-Crossover Formation
Commentary 501 The choice in meiosis – defining the factors that influence crossover or non-crossover formation Jillian L. Youds and Simon J. Boulton* DNA Damage Response Laboratory, Cancer Research UK, London Research Institute, Clare Hall, Blanche Lane, South Mimms EN6 3LD, UK *Author for correspondence ([email protected]) Journal of Cell Science 124, 501-513 © 2011. Published by The Company of Biologists Ltd doi:10.1242/jcs.074427 Summary Meiotic crossovers are essential for ensuring correct chromosome segregation as well as for creating new combinations of alleles for natural selection to take place. During meiosis, excess meiotic double-strand breaks (DSBs) are generated; a subset of these breaks are repaired to form crossovers, whereas the remainder are repaired as non-crossovers. What determines where meiotic DSBs are created and whether a crossover or non-crossover will be formed at any particular DSB remains largely unclear. Nevertheless, several recent papers have revealed important insights into the factors that control the decision between crossover and non-crossover formation in meiosis, including DNA elements that determine the positioning of meiotic DSBs, and the generation and processing of recombination intermediates. In this review, we focus on the factors that influence DSB positioning, the proteins required for the formation of recombination intermediates and how the processing of these structures generates either a crossover or non-crossover in various organisms. A discussion of crossover interference, assurance and homeostasis, which influence crossing over on a chromosome-wide and genome-wide scale – in addition to current models for the generation of interference – is also included. This Commentary aims to highlight recent advances in our understanding of the factors that promote or prevent meiotic crossing over. -
Homologs in Saccharomyces Cerevisiae but Not Mismatch Repair
Downloaded from genesdev.cshlp.org on October 1, 2021 - Published by Cold Spring Harbor Laboratory Press MSH5, a novel MutS homolog, facilitates meiotic reciprocal recombination between homologs in Saccharomyces cerevisiae but not mismatch repair Nancy Marie Hollingsworth, 1 Lisa Ponte, and Carol Halsey Department of Biochemistry and Cell Biology, State University of New York, Stony Brook, Stony Brook, New York 11794-5215 USA Using a screen designed to identify yeast mutants specifically defective in recombination between homologous chromosomes during meiosis, we have obtained new alleles of the meiosis-specific genes, HOP1, RED1, and MEK1. In addition, the screen identified a novel gene designated MSH5 (MutS homolog 51. Although Msh5p exhibits strong homology to the MutS family of proteins, it is not involved in DNA mismatch repair. Diploids lacking the MSH5 gene display decreased levels of spore viability, increased levels of meiosis I chromosome nondisjunction, and decreased levels of reciprocal exchange between, but not within, homologs. Gene conversion is not reduced. Msh5 mutants are phenotypicaUy similar to mutants in the meiosis-specific gene MSH4 (Ross-Macdonald and Roeder 1994}. Double mutant analysis using rash4 rash5 diploids demonstrates that the two genes are in the same epistasis group and therefore are likely to function in a similar process--namely, the facilitation of interhomolog crossovers during meiosis. [Key Words: MSH5; yeast; MutS homolog; recombination] Received March 9, 1995; revised version accepted June 6, 1995. A unique problem confronting sexually reproducing or- ated in the presence of SCs, it is necessary to first define ganisms is how to maintain the parental chromosome the proteins involved both in synapsis (i.e., SC forma- number in offspring produced by fertilization. -
Coding and Noncoding Variants in HFM1, MLH3, MSH4, MSH5, RNF212, and RNF212B Affect Recombination Rate in Cattle
Downloaded from genome.cshlp.org on September 29, 2021 - Published by Cold Spring Harbor Laboratory Press Research Coding and noncoding variants in HFM1, MLH3, MSH4, MSH5, RNF212, and RNF212B affect recombination rate in cattle Naveen Kumar Kadri,1 Chad Harland,1,2 Pierre Faux,1 Nadine Cambisano,1,3 Latifa Karim,1,3 Wouter Coppieters,1,3 Sébastien Fritz,4,5 Erik Mullaart,6 Denis Baurain,7 Didier Boichard,5 Richard Spelman,2 Carole Charlier,1 Michel Georges,1 and Tom Druet1 1Unit of Animal Genomics, GIGA-R & Faculty of Veterinary Medicine, University of Liège (B34), 4000 Liège, Belgium; 2Livestock Improvement Corporation, Newstead, 3240 Hamilton, New Zealand; 3Genomics Platform, GIGA, University of Liège (B34), 4000 Liège, Belgium; 4Allice, 75012 Paris, France; 5GABI, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France; 6CRV BV, 6800 AL Arnhem, the Netherlands; 7InBioS-Eukaryotic Phylogenomics, Department of Life Sciences and PhytoSYSTEMS, University of Liège (B22), 4000 Liège, Belgium We herein study genetic recombination in three cattle populations from France, New Zealand, and the Netherlands. We identify 2,395,177 crossover (CO) events in 94,516 male gametes, and 579,996 CO events in 25,332 female gametes. The average number of COs was found to be larger in males (23.3) than in females (21.4). The heritability of global recombi- nation rate (GRR) was estimated at 0.13 in males and 0.08 in females, with a genetic correlation of 0.66 indicating that shared variants are influencing GRR in both sexes. A genome-wide association study identified seven quantitative trait loci (QTL) for GRR. -
A Mutation in the MSH5 Gene Results in Alkylation Tolerance1
[CANCERRESEARCH57,2715—2720,July1. l997J A Mutation in the MSH5 Gene Results in Alkylation Tolerance1 Sonya Bawa and Wei Xiao2 Department of Microbiology, University of Saskatchewan, 107 Wiggins Road, Saskatoon, Saskatchewan S7N 5E5, Canada ABSTRACT results in the accumulation of single-stranded nicks in DNA, which are ultimately lethal to the cell. This hypothesis is attractive not only DNA methylating agents such as N-methyl-N'-nitro-N-nitrosoguanidine because it provides an alternative to 06 MeG/O4 MeT genotoxicity (MNNG)are potent carcinogens;their carcinogeniceffectis mainlydue to but also because genetic defects in several human MMR genes have the effect of production of O'-methylguanine (06 MeG) on DNA. 06 MeG is not only mutagenic but also toxic to the cell because Mer/Mex cells been linked to hereditary nonpolyposis colon cancer as well as other unable to remove O@MeG are very sensitive to killing by MNNG. It has types of cancers (9—14).However, the abortive MMR hypothesis been proposed that repeated futile mismatch correction of 06 MeG should be viewed with caution because the current supporting cvi containing bp is responsible for the genotoxicity of the O@MeG lesion and dence with mammalian cells is not conclusive and a convenient that loss of mismatch repair activity results in cellular tolerance to 06 mammalian system is not available to vigorously test the hypothesis. MeG, but the hypothesis has not been proved. We used yeast as a model The MMR system consisting of Escherichia coli MutS and MutL to test this hypothesis and found that chromosome deletion of any known homologues has been extensively studied recently in yeast and human nuclear mitotic mismatch repair genes, including MUll, MSH2, MSH3, cells (reviewed in Refs. -
Caspase Activation & Apoptosis
RnDSy-lu-2945 Caspase Activation & Apoptosis Extrinsic & Intrinsic Pathways of Caspase Activation CASPASE CLEAVAGE & ACTIVATION Caspases are a family of aspartate-specific, cysteine proteases that serve as the primary mediators of Pro-Domain Large Subunit (p20) Small Subunit (p10) apoptosis. Mammalian caspases can be subdivided into three functional groups, apoptotic initiator TRAIL Pro-Domain α chain β chain caspases (Caspase-2, -8, -9, -10), apoptotic effector caspases (Caspase-3, -6, -7), and caspases involved Asp-x Asp-x Proteolytic cleavage in inflammatory cytokine processing (Caspase-1, -4, -5, 11, and -12L/12S). All caspases are synthesized α chain as inactive zymogens containing a variable length pro-domain, followed by a large (20 kDa) and a small Fas Ligand TRAIL R1 Pro-Domain β chain TRAIL R2 Heterotetramer Formation (10 kDa) subunit. FADD FADD α chain α chain Pro-caspase-8, -10 Active caspase Pro-caspase-8, -10 TWEAK β chain Apoptotic caspases are activated upon the receipt of either an extrinsic or an intrinsic death signal. The Fas/CD95 extrinsic pathway (green arrows) is initiated by ligand binding to cell surface death receptors (TNF RI, Fas/ MAMMALIAN CASPASE DOMAINS & CLEAVAGE SITES FADD FADD TNF-α APOPTOTIC CASPASES CD95, DR3, TRAIL R1/DR4, TRAIL R2/DR5) followed by receptor oligomerization and cleavage of Pro- Extrinsic Pathway DR3 (or another TWEAK R) INITIATOR CASPASES 152 316 331 Pro-caspase-8, -10 Pro-caspase-8, -10 1 435 caspase-8 and -10. Activation of Caspase-8 and Caspase-10 results in the cleavage of BID and Caspase-2 CARD TRADD FLIP TRADD downstream effector caspases. -
The Many Facets of SC Function During C. Elegans Meiosis
Chromosoma DOI 10.1007/s00412-006-0061-9 REVIEW Mónica P. Colaiácovo The many facets of SC function during C. elegans meiosis Received: 7 December 2005 / Revised: 15 February 2006 / Accepted: 16 February 2006 # Springer-Verlag 2006 Abstract Sexually reproducing organisms rely on meiosis halving in chromosome number is the result of one round for the formation of haploid gametes. This is achieved of DNA replication followed by two rounds of cell through two consecutive rounds of cell division (meiosis I division: meiosis I (a reductional division) and meiosis II and II) after one round of DNA replication. During the (an equational division). While meiosis II proceeds meiotic divisions, chromosomes face several challenges to similarly to a mitotic division, unique events unfold during ultimately ensure proper chromosome segregation. Unique meiosis I. In particular, during prophase I, homologous events unfold during meiosis I to overcome these chromosomes have to identify each other and pair, challenges. Homologous chromosomes pair, synapse, and followed by the formation of a proteinaceous structure recombine. A remarkable feature throughout this process is known as the synaptonemal complex (SC) between the formation of an evolutionarily conserved tripartite homologs, and completion of meiotic recombination proteinaceous structure known as the synaptonemal com- leading to physical attachments between homologs. plex (SC). It is comprised of two lateral elements, These events ultimately ensure proper chromosome segre- assembled along each axis of a pair of homologous gation upon the first meiotic division. Succeeding in this chromosomes, and a central region consisting of transverse outcome is crucial given that chromosome nondisjunction filaments bridging the gap between lateral elements. -
MSH5) Reveals a Requirement for a Functional Mutsg Complex for All Crossovers in Mammalian Meiosis
INVESTIGATION Mutation of the ATPase Domain of MutS Homolog-5 (MSH5) Reveals a Requirement for a Functional MutSg Complex for All Crossovers in Mammalian Meiosis Carolyn R. Milano,* J. Kim Holloway,* Yongwei Zhang,† Bo Jin,† Cameron Smith,‡ Aviv Bergman,‡ Winfried Edelmann,†,1 and Paula E. Cohen*,1 *Department of Biomedical Sciences and Center for Reproductive Genomics, Cornell University, Ithaca, NY 14853, †Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, and ‡Department of Systems and Computational Biology, Albert Einstein College of Medicine, Bronx, NY 10461 ORCID IDs: 0000-0003-1261-3763 (C.R.M.); 0000-0002-2050-6979 (P.E.C.) ABSTRACT During meiosis, induction of DNA double strand breaks (DSB) leads to recombination between KEYWORDS homologous chromosomes, resulting in crossovers (CO) and non-crossovers (NCO). In the mouse, only 10% of MutS homolog DSBs resolve as COs, mostly through a class I pathway dependent on MutSg (MSH4/ MSH5) and MutLg meiosis (MLH1/MLH3), the latter representing the ultimate marker of these CO events. A second Class II CO pathway mouse accounts for only a few COs, but is not thought to involve MutSg/ MutLg, and is instead dependent on crossing over MUS81-EME1. For class I events, loading of MutLg is thought to be dependent on MutSg,howeverMutSg homologous loads very early in prophase I at a frequency that far exceeds the final number of class I COs. Moreover, loss of recombination MutSg in mouse results in apoptosis before CO formation, preventing the analysis of its CO function. We crossover generated a mutation in the ATP binding domain of Msh5 (Msh5GA).