DOCSLIB.ORG

Modulating Crossover Frequency and Interference for Obligate Crossovers in Saccharomyces Cerevisiae Meiosis

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Modulating Crossover Frequency and Interference for Obligate Crossovers in Saccharomyces Cerevisiae Meiosis INVESTIGATION Modulating Crossover Frequency and Interference for Obligate Crossovers in Saccharomyces cerevisiae Meiosis Parijat Chakraborty,* Ajith V. Pankajam,* Gen Lin,† Abhishek Dutta,* Krishnaprasad G. Nandanan,* Manu M. Tekkedil,† Akira Shinohara,‡ Lars M. Steinmetz,†,§,** and Nishant K. Thazath*,††,1 *School of Biology and ††Center for Computation, Modelling and Simulation, Indian Institute of Science Education and Research, Thiruvananthapuram, Trivandrum 695016, India, †Genome Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany, ‡Institute for Protein Research, Osaka University, 565-0871, Japan, § Department of Genetics, Stanford University, California 94305, and **Stanford Genome Technology Center, Palo Alto, California 94304 ABSTRACT Meiotic crossover frequencies show wide variation among organisms. But most organisms maintain KEYWORDS at least one crossover per homolog pair (obligate crossover). In Saccharomyces cerevisiae, previous studies have crossover shown crossover frequencies are reduced in the mismatch repair related mutant mlh3D and enhanced in a frequency meiotic checkpoint mutant pch2D by up to twofold at specific chromosomal loci, but both mutants maintain high crossover spore viability. We analyzed meiotic recombination events genome-wide in mlh3D, pch2D,andmlh3D pch2D assurance mutants to test the effect of variation in crossover frequency on obligate crossovers. mlh3D showed 30% meiotic genome-wide reduction in crossovers (64 crossovers per meiosis) and loss of the obligate crossover, but non- chromosome exchange chromosomes were efficiently segregated. pch2D showed 50% genome-wide increase in crossover segregation frequency (137 crossovers per meiosis), elevated noncrossovers as well as loss of chromosome size dependent genetic double-strand break formation. Meiotic defects associated with pch2Δ did not cause significant increase in interference nonexchange chromosome frequency. Crossovers were restored to wild-type frequency in the double mutant genome wide mlh3D pch2D (100 crossovers per meiosis), but obligate crossovers were compromised. Genetic interference recombination was reduced in mlh3D, pch2D,andmlh3D pch2D. Triple mutant analysis of mlh3D pch2D with other resolvase map mutants showed that most of the crossovers in mlh3D pch2D are made through the Mus81-Mms4 pathway. These results are consistent with a requirement for increased crossover frequencies in the absence of genetic interference for obligate crossovers. In conclusion, these data suggest crossover frequencies and the strength of genetic interference in an organism are mutually optimized to ensure obligate crossovers. Meiosis is a reductional division that produces haploid gametes or spores (Meiosis I and II), producing four daughter cells (Roeder 1997). Cross- from diploid progenitor cells. Ploidy reduction is achieved by one round overs promote the formation of chiasma which serves as a physical of DNA replication, followed by two consecutive nuclear divisions linkage between two homologs and opposes the spindle generated forces that pull apart the homolog pairs. This opposing set of forces Copyright © 2017 Chakraborty et al. provides the tension necessary to promote proper disjunction of ho- doi: https://doi.org/10.1534/g3.117.040071 molog pairs at Meiosis I (Petronczki et al. 2003). Failure to maintain at Manuscript received November 16, 2016; accepted for publication March 12, 2017; least one crossover per homolog pair increases the probability of non- published Early Online March 17, 2017. disjunction, resulting in aneuploid gametes (Serrentino and Borde This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/ 2012). Although crossovers are important for chromosome segregation, licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction nonexchange chromosomes have been observed to segregate accurately in any medium, provided the original work is properly cited. forming viable gametes (Hawley et al. 1992; Davis and Smith 2003; Supplemental material is available online at www.g3journal.org/lookup/suppl/ Kemp et al. 2004; Newnham et al. 2010; Krishnaprasad et al. 2015). doi:10.1534/g3.117.040071/-/DC1. 1 Meiotic crossovers (and noncrossovers) are initiated in S. cerevisiae Corresponding author: School of Biology, Indian Institute of Science Education – and Research, Thiruvananthapuram, CET Campus, Trivandrum 695016, India. by 150 170 programmed double-strand breaks (DSBs) formed by an E-mail: [email protected] evolutionarily conserved topoisomerase-like protein Spo11 and other Volume 7 | May 2017 | 1511 accessory proteins (reviewed in Neale and Keeney 2006). The frequency msh4D,andmsh5D) (Sym and Roeder 1994; Nakagawa and Ogawa and distribution of crossovers on chromosomes is a tightly regulated 1999; Novak et al. 2001; Argueso et al. 2004; Zakharyevich et al. 2012), process. Four known aspects of this regulation are crossover interfer- but the distribution of Zip3 foci (measured in physical distances), which ence, obligate crossovers, crossover homeostasis, and crossover invari- mark DSB sites designated to be repaired as crossovers, show interfer- ance. Crossover interference regulates the spatial patterning of ence in zip1D and msh4D mutants (Zhang et al. 2014). crossovers, where the presence of a crossover prevents the formation It is not clear why organisms have vastly different crossover fre- of a second crossover in its vicinity. As a consequence, an even distri- quencies and how this is related to ensuring an obligate crossover. In this bution of crossovers is ensured, and closely spaced crossovers are less study, we address the relationship of obligate crossovers with crossover frequently observed than expected from a random distribution frequency using mlh3D and pch2D mutants. In S. cerevisiae,boththese (Berchowitz and Copenhaver 2010). An obligate crossover per homo- mutants have very different crossover frequencies but show high spore log pair facilitates disjunction. The obligate crossover is not a specific viability. At specific chromosomal loci, mlh3D shows up to a 50% re- type of crossover, but refers to the observation that process(es) that duction in crossover frequency but with good spore viability ranging generate most of the crossovers result in at least one crossover per from 72% and up to 92% depending on the strain background (Nishant homolog pair (Barchi et al. 2008). The obligate crossovers are ensured et al. 2008; Cotton et al. 2010; Sonntag Brown et al. 2013). Pch2 is an in different organisms with different crossover frequencies. For exam- evolutionarily conserved hexameric ring AAA+ ATPase protein that ple, organisms that have strong genetic interference like Caenorhabditis has roles in meiotic checkpoint signaling triggered by unrepaired DSBs, elegans, Drosophila, Arabidopsis, mouse, and humans ensure obligate remodeling the chromosome axis at the future crossover sites and crossovers, although the number of crossovers per bivalent pair is low interhomolog bias (San-Segundo and Roeder 1999; Borner et al. (1–2) (Copenhaver et al. 2002; Hillers and Villeneuve 2003; 2008; Ho and Burgess 2011; Zanders et al. 2011; Chen et al. 2014). Berchowitz and Copenhaver 2010; Libuda et al. 2013). But organisms pch2D mutants are observed to make 50% more crossovers than wild with weaker interference, like S. cerevisiae,make90 crossovers, or 6 type at specific loci, and also have good viability (95%) (Zanders and times the number of bivalent pairs (16), to ensure an obligate event. Alani 2009; but see Joshi et al. 2009). The mlh3D and pch2D mutants Crossover homeostasis ensures that the number of crossovers is main- are therefore useful to test the effect of a wide range of crossover tained (at the expense of noncrossovers) when the DSB precursors frequencies on obligate crossovers. It is important to note that pleio- become limiting (Martini et al. 2006). This crossover buffering mech- tropic effects of pch2D could affect the interpretation of changes in anism is also seen when the DSBs are increased (Cole et al. 2012). crossover frequencies on the obligate crossover. Crossover invariance is another mechanism that maintains the number We performed genome-wide mapping of meiotic recombination of crossovers in organisms that lack interference. This phenomenon events in mlh3D, pch2D and mlh3D pch2D using the S288c/YJM789 refers to the observation that, in Schizosaccharomyces pombe,theratio hybrid. Crossovers in all three mutants, mlh3D (64 crossovers per of intersister to interhomolog repair is modulated in response to var- meiosis on average), pch2D (137 crossovers per meiosis on average) iations in DSB intensity to ensure uniform crossover distribution and mlh3D pch2D (100 crossovers per meiosis on average) showed (Hyppa and Smith 2010). Recent studies suggest crossover interference, reduced genetic interference. Noncrossovers were not affected in obligate crossovers, and crossover homeostasis are the outcomes of a mlh3D, but increased in pch2D and mlh3D pch2D. Crossover and non- single crossover patterning process regulated by the “mechanical stress crossover data suggest loss of chromosome size dependent DSB forma- relief” of chromosomes (Wang et al. 2015; Zickler and Kleckner 2016). tion in pch2D mutants. mlh3D pch2D showed uniform crossover As per this model, crossover interference and homeostasis are linked density on all chromosomes consistent with loss of genetic
Load more

Recommended publications
  • Human Cell Assays for Synthesis-Dependent Strand Annealing and Crossing Over During Double-Strand Break Repair
    INVESTIGATIONS Human Cell Assays for Synthesis-Dependent Strand Annealing and Crossing Over During Double-Strand Break Repair Grzegorz Zapotoczny∗,1 and Jeff Sekelsky∗ † ‡,1 ∗Curriculum in Genetics and Molecular Biology, †Department of Biology, ‡Integrative Program for Biological and Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA ABSTRACT DNA double-strand breaks (DSBs) are one of the most deleterious types of lesions to the genome. KEYWORDS Synthesis-dependent strand annealing (SDSA) is thought to be a major pathway of DSB repair, but direct tests double-strand of this model have only been conducted in budding yeast and Drosophila. To better understand this pathway, break repair we developed an SDSA assay for use in human cells. Our results support the hypothesis that SDSA is an crossing over important DSB repair mechanism in human cells. We used siRNA knockdown to assess the roles of a number synthesis- of helicases suggested to promote SDSA. None of the helicase knockdowns reduced SDSA, but knocking dependent down BLM or RTEL1 increased SDSA. Molecular analysis of repair products suggest that these helicases may strand annealing prevent long-tract repair synthesis. Since the major alternative to SDSA – repair involving a double-Holliday junction intermediate – can lead to crossovers, we also developed a fluorescent assay that detects crossovers generated during DSB repair. Together, these assays will be useful in investigating features and mechanisms of SDSA and crossover pathways in human cells. link (Figure1)(Thaler et al. 1987); this process has been called INTRODUCTION dissolution to distinguish it from endonucleolytic resolution (Wu and Hickson 2003).
    [Show full text]
  • Perspectives
    Copyright Ó 2008 by the Genetics Society of America Perspectives Anecdotal, Historical and Critical Commentaries on Genetics Edited by James F. Crow and William F. Dove The Phage Mating Theory, With Lessons for Yeast Geneticists Frank Stahl1 Institute of Molecular Biology, University of Oregon, Eugene, Oregon 97403-1229 HEN physicist Max Delbru¨ck undertook the study sistance to the possibility of genetic recombination with W of phage growth (Ellis and Delbru¨ck 1939), he its implications of sexual reproduction and the variety of anticipated that phage would be the best model for highly evolved stuff that so often goes with it (Delbru¨ck elucidating biological reproduction and mutation, un- and Bailey 1947). complicated by sex (Delbru¨ck 1970). This Perspectives However, Max’s hopes for simplicity were soon chal- traces Max’s attempt to come to grips with realities that lenged again by the results and interpretation of experi- threatened that view, and it considers present-day rel- ments conducted with UV-inactivated phages (Luria evanceforyeastgeneticistsoftwolessonsthatremainfrom 1947; Luria and Dulbecco 1949). The UV experiments his heroic effort. showed that phage particles killed by irradiation could Readers should understand (or recall) that in 1939 cooperate to produce live phage, a trick that was labeled essentially nothing of what we now know about the ‘‘multiplicity reactivation’’ (MR) because this cooper- chemistry of either reproduction or mutation was even ation required that a bacterial cell be infected with two imagined—for nucleic acids, it was ‘‘known’’ only that or more phage particles. Luria and Dulbecco (1949) most of the DNA is in the nucleus and most of the RNA is collected MR data for a range of UV doses and a variety of in the cytoplasm and, for proteins, only that some were multiplicities and found that the data could be fitted to a enzymes and that they were probably the stuff that genes mathematically expressed theory.
    [Show full text]
  • Meiotic Recombination and Its Implications for Plant Breeding
    Meiotic recombination and its implications for plant breeding T.G. (Erik) Wijnker Thesis committee Promotors Prof. dr. J.H.S.G.M. de Jong Personal chair at the Laboratory of Genetics, Wageningen University Prof. dr. ir. M. Koornneef Personal chair at the Laboratory of Genetics, Wageningen University and Director at the Max Planck Institute for Plant Breeding Research (MPIZ) Cologne, Germany Co-promotor Dr. R.H.G. Dirks Research manager at the Rijk Zwaan Breeding Company, Fijnaart. Other members Prof. dr. ir. E. Jacobsen, Wageningen University, Wageningen Prof. dr. H. Puchta, University of Karlsruhe, Karlsruhe, Germany Dr. A. Schnittger, University of Strasbourg, Strasbourg, France Prof. dr. M.E. Schranz, Wageningen University, Wageningen This research was conducted under the auspices of the Graduate School Experimental Plant Sciences (EPS) Meiotic recombination and its implications for plant breeding T.G. (Erik) Wijnker Thesis at Wageningen University Submitted in fulfillment of the requirements for the degree of doctor Prof. dr. M.J. Kropf, by the authorityin the presence of the Rector of the Magnificus Thesis Committee appointed by the Academic Board to be defended in public on Wednesday 6 February 2013 at 4 p.m. in the Aula. T.G. (Erik) Wijnker Meiotic Recombination and its implications for plant breeding With references, with summaries in Dutch and English Thesis, Wageningen University, Wageningen, NL (2013) ISBN 978-94-6173-440-2 Contents General introduction Chapter 1 7 Whole-genome sequencing of (non–)crossover sites reveals that
    [Show full text]
  • 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.
    [Show full text]
  • 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.
    [Show full text]
  • Insights Into Regulation of Human RAD51 Nucleoprotein Filament Activity During
    Insights into Regulation of Human RAD51 Nucleoprotein Filament Activity During Homologous Recombination Dissertation Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Ravindra Bandara Amunugama, B.S. Biophysics Graduate Program The Ohio State University 2011 Dissertation Committee: Richard Fishel PhD, Advisor Jeffrey Parvin MD PhD Charles Bell PhD Michael Poirier PhD Copyright by Ravindra Bandara Amunugama 2011 ABSTRACT Homologous recombination (HR) is a mechanistically conserved pathway that occurs during meiosis and following the formation of DNA double strand breaks (DSBs) induced by exogenous stresses such as ionization radiation. HR is also involved in restoring replication when replication forks have stalled or collapsed. Defective recombination machinery leads to chromosomal instability and predisposition to tumorigenesis. However, unregulated HR repair system also leads to similar outcomes. Fortunately, eukaryotes have evolved elegant HR repair machinery with multiple mediators and regulatory inputs that largely ensures an appropriate outcome. A fundamental step in HR is the homology search and strand exchange catalyzed by the RAD51 recombinase. This process requires the formation of a nucleoprotein filament (NPF) on single-strand DNA (ssDNA). In Chapter 2 of this dissertation I describe work on identification of two residues of human RAD51 (HsRAD51) subunit interface, F129 in the Walker A box and H294 of the L2 ssDNA binding region that are essential residues for salt-induced recombinase activity. Mutation of F129 or H294 leads to loss or reduced DNA induced ATPase activity and formation of a non-functional NPF that eliminates recombinase activity. DNA binding studies indicate that these residues may be essential for sensing the ATP nucleotide for a functional NPF formation.
    [Show full text]
  • Branching Out: Meiotic Recombination and Its Regulation
    TICB-453; No of Pages 8 Review TRENDS in Cell Biology Vol.xxx No.x Branching out: meiotic recombination and its regulation Gareth A. Cromie and Gerald R. Smith Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109-1024, USA Homologous recombination is a dynamic process by parental chromosome segregation during the first meiotic which DNA sequences and strands are exchanged. In division. The COs link the homologous chromosomes phy- meiosis, the reciprocal DNA recombination events called sically so that they can be oriented correctly on the meiotic crossovers are central to the generation of genetic diver- spindle. In the absence of COs, chromosomes often mis- sity in gametes and are required for homolog segregation segregate, resulting in aneuploid gametes and offspring. in most organisms. Recent studies have shed light on how Recent studies have advanced our understanding of how meiotic crossovers and other recombination products meiotic COs and NCOs form, how they are distributed form, how their position and number are regulated and across genomes, and how the pair of DNA molecules under- how the DNA molecules undergoing recombination are going a CO is chosen. In this review, we focus on how chosen. These studies indicate that the long-dominant, advances in these three areas have challenged several core unifying model of recombination proposed by Szostak features of long-accepted models, revealing many new et al. applies, with modification, only to a subset of branches of the meiotic recombination ‘pathway’. Most recombination events. Instead, crossover formation and significantly, the mechanism of recombination associated its control involve multiple pathways, with considerable with the well-known DSB repair model of Szostak et al.
    [Show full text]
  • Human Muts Homologue MSH4 Physically Interacts with Von Hippel-Lindau Tumor Suppressor-Binding Protein 11
    [CANCER RESEARCH 63, 865–872, February 15, 2003] Human MutS Homologue MSH4 Physically Interacts with von Hippel-Lindau Tumor Suppressor-binding Protein 11 Chengtao Her,2 Xiling Wu, Michael D. Griswold, and Feng Zhou School of Molecular Biosciences and Center for Reproductive Biology, Washington State University, Pullman, Washington 99164-4660 [C. H., X. W., M. D. G.], and Bioscience Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545 [F. Z.] ABSTRACT human MMR genes are linked to the pathogenesis of hereditary nonpolyposis colorectal cancer (HNPCC) and sporadic tumors Increasing evidence indicated that the protein factors involved in DNA associated with microsatellite instability (1). Eukaryotic MutS mismatch repair (MMR) possess meiotic functions beyond the scope of DNA mismatch correction. The important roles of MMR components in homologous proteins MSH2, MSH3, and MSH6 are proteins meiotic processes have been highlighted by the recent identification of two known to participate in DNA MMR through the actions of their additional members of the mammalian MutS homologs, MSH4 and heterodimeric complexes consisting of either MSH2-MSH3 or MSH5. Mammalian MSH4 and MSH5 proteins form a heterodimeric MSH2-MSH6, in which the MSH2-MSH6 heterodimer recognizes complex and play an important role in the meiotic processes. As a step both single-base mismatches and small loops formed by insertions forward to the understanding of the molecular mechanisms underlying or deletions in the DNA, whereas the MSH2-MSH3 heterodimer the roles of these two mammalian MutS homologues, here we have iden- only recognizes small insertions and deletions (3, 4). tified von Hippel-Lindau (VHL) tumor suppressor-binding protein 1 Recent evidence demonstrates that eukaryotes contained a sep- (VBP1) as an interacting protein partner for human MSH4 (hMSH4).
    [Show full text]
  • Genetics of Azoospermia
    International Journal of Molecular Sciences Review Genetics of Azoospermia Francesca Cioppi , Viktoria Rosta and Csilla Krausz * Department of Biochemical, Experimental and Clinical Sciences “Mario Serio”, University of Florence, 50139 Florence, Italy; francesca.cioppi@unifi.it (F.C.); viktoria.rosta@unifi.it (V.R.) * Correspondence: csilla.krausz@unifi.it Abstract: Azoospermia affects 1% of men, and it can be due to: (i) hypothalamic-pituitary dysfunction, (ii) primary quantitative spermatogenic disturbances, (iii) urogenital duct obstruction. Known genetic factors contribute to all these categories, and genetic testing is part of the routine diagnostic workup of azoospermic men. The diagnostic yield of genetic tests in azoospermia is different in the different etiological categories, with the highest in Congenital Bilateral Absence of Vas Deferens (90%) and the lowest in Non-Obstructive Azoospermia (NOA) due to primary testicular failure (~30%). Whole- Exome Sequencing allowed the discovery of an increasing number of monogenic defects of NOA with a current list of 38 candidate genes. These genes are of potential clinical relevance for future gene panel-based screening. We classified these genes according to the associated-testicular histology underlying the NOA phenotype. The validation and the discovery of novel NOA genes will radically improve patient management. Interestingly, approximately 37% of candidate genes are shared in human male and female gonadal failure, implying that genetic counselling should be extended also to female family members of NOA patients. Keywords: azoospermia; infertility; genetics; exome; NGS; NOA; Klinefelter syndrome; Y chromosome microdeletions; CBAVD; congenital hypogonadotropic hypogonadism Citation: Cioppi, F.; Rosta, V.; Krausz, C. Genetics of Azoospermia. 1. Introduction Int. J. Mol. Sci.
    [Show full text]
  • 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.
    [Show full text]
  • Crossing and Zipping: Molecular Duties of the ZMM Proteins in Meiosis Alexandra Pyatnitskaya, Valérie Borde, Arnaud De Muyt
    Crossing and zipping: molecular duties of the ZMM proteins in meiosis Alexandra Pyatnitskaya, Valérie Borde, Arnaud de Muyt To cite this version: Alexandra Pyatnitskaya, Valérie Borde, Arnaud de Muyt. Crossing and zipping: molecular duties of the ZMM proteins in meiosis. Chromosoma, Springer Verlag, 2019, 10.1007/s00412-019-00714-8. hal-02413016 HAL Id: hal-02413016 https://hal.archives-ouvertes.fr/hal-02413016 Submitted on 16 Dec 2019 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Manuscript Click here to access/download;Manuscript;review ZMM Chromosoma2019_Revised#2.docx Click here to view linked References Crossing and zipping: molecular duties of the ZMM proteins in meiosis 1 2 3 1,2 1,2,* 1,2,* 4 Alexandra Pyatnitskaya , Valérie Borde and Arnaud De Muyt 5 1 Institut Curie, PSL Research University, CNRS, UMR3244, Paris, France. 6 7 2 Paris Sorbonne Université, Paris, France. 8 9 *Valérie Borde, [email protected]; Arnaud De Muyt, [email protected] 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 Keywords : meiosis, crossover, recombination, synaptonemal complex, ZMM 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 1 65 Abstract 1 2 Accurate segregation of homologous chromosomes during meiosis depends on the ability 3 4 of meiotic cells to promote reciprocal exchanges between parental DNA strands, known 5 as crossovers (COs).
    [Show full text]
  • 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.
    [Show full text]