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Genome Rearrangements Caused By Interstitial Telomeric Sequences In Yeast

Anna Y Aksenova, P. Greenwell, M. Dominska, A. Shishkin, Jane C. Kim, T. Petes, S. Mirkin
Published 2013 · Biology, Medicine

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Significance Telomeres are composed of simple repetitive DNA sequences that normally are located at the ends of the chromosomes. Occasionally, however, they also are found inside chromosomes. Some of these internal or interstitial telomeric sequences colocalize with chromosomal fragile sites, preferred sites of breakage in some cancers and hereditary human diseases. The mechanisms responsible for genome instability at interstitial telomeric sequences are unclear. We developed a system to study genetic instabilities caused by these sequences in a model organism (baker’s yeast) that allowed us to characterize various chromosomal rearrangements and to measure the likelihood of their formation. We found that interstitial telomeric sequences promote the formation of deletions, duplications, inversions, and translocations, and we proposed molecular mechanisms responsible for these events. Interstitial telomeric sequences (ITSs) are present in many eukaryotic genomes and are linked to genome instabilities and disease in humans. The mechanisms responsible for ITS-mediated genome instability are not understood in molecular detail. Here, we use a model Saccharomyces cerevisiae system to characterize genome instability mediated by yeast telomeric (Ytel) repeats embedded within an intron of a reporter gene inside a yeast chromosome. We observed a very high rate of small insertions and deletions within the repeats. We also found frequent gross chromosome rearrangements, including deletions, duplications, inversions, translocations, and formation of acentric minichromosomes. The inversions are a unique class of chromosome rearrangement involving an interaction between the ITS and the true telomere of the chromosome. Because we previously found that Ytel repeats cause strong replication fork stalling, we suggest that formation of double-stranded DNA breaks within the Ytel sequences might be responsible for these gross chromosome rearrangements.
This paper references
Hypermutability of Damaged Single-Strand DNA Formed at Double-Strand Breaks and Uncapped Telomeres in Yeast Saccharomyces cerevisiae
Y. Yang (2008)
Everything You Ever Wanted to Know About Saccharomyces cerevisiae Telomeres: Beginning to End
R. Wellinger (2012)
Role of DNA polymerases in repeat-mediated genome instability.
K. Shah (2012)
Replication stalling at unstable inverted repeats: Interplay between DNA hairpins and fork stabilizing proteins
I. Voineagu (2008)
Fragile DNA Motifs Trigger Mutagenesis at Distant Chromosomal Loci in Saccharomyces cerevisiae
Natalie Saini (2013)
The human TTAGGG repeat factors 1 and 2 bind to a subset of interstitial telomeric sequences and satellite repeats
T. Simonet (2011)
Double-strand break end resection and repair pathway choice.
L. Symington (2011)
Mrc1 and Tof1 regulate DNA replication forks in different ways during normal S phase.
B. Hodgson (2007)
Rad52-independent mitotic gene conversion in Saccharomyces cerevisiae frequently results in chromosomal loss.
J. Haber (1985)
Position effect at S. cerevisiae telomeres: Reversible repression of Pol II transcription
D. Gottschling (1990)
Replication Stalling at Friedreich's Ataxia (GAA)n Repeats In Vivo
M. Krasilnikova (2004)
Internal tracts of telomeric DNA act as silencers in Saccharomyces cerevisiae.
J. Stavenhagen (1994)
Insertion of a Telomere Repeat Sequence into a Mammalian Gene Causes Chromosome Instability
A. Kilburn (2001)
Large-scale expansions of Friedreich's ataxia GAA repeats in yeast.
A. Shishkin (2009)
Fusion of nearby inverted repeats by a replication-based mechanism leads to formation of dicentric and acentric chromosomes that cause genome instability in budding yeast.
Andrew L Paek (2009)
Replication Stress-Induced Chromosome Breakage Is Correlated with Replication Fork Progression and Is Preceded by Single-Stranded DNA Formation
W. Feng (2011)
Inhibition of Silencing and Accelerated Aging by Nicotinamide, a Putative Negative Regulator of Yeast Sir2 and Human SIRT1*
Kevin J. Bitterman (2002)
Contribution of telomerase RNA retrotranscription to DNA double-strand break repair during mammalian genome evolution
S. Nergadze (2007)
Overcoming natural replication barriers: differential helicase requirements
R. Anand (2012)
Chromosome fragility at GAA tracts in yeast depends on repeat orientation and requires mismatch repair
Hyunmin Kim (2008)
Spontaneous and radiation-induced chromosomal breakage at interstitial telomeric sites
P. Slijepcevic (2004)
Genomic instability in rat: breakpoints induced by ionising radiation and interstitial telomeric-like sequences.
N. Camats (2006)
Endings in the middle: current knowledge of interstitial telomeric sequences.
K. W. Lin (2008)
Chromosomal Translocations in Yeast Induced by Low Levels of DNA Polymerase A Model for Chromosome Fragile Sites
Francene J. Lemoine (2005)
Co-segregation of yeast plasmid sisters under monopolin-directed mitosis suggests association of plasmid sisters with sister chromatids
Yen-Ting Liu (2013)
Double-strand break end resection and repair pathway
LS Symington (2011)
A Genetic and Structural Study of Genome Rearrangements Mediated by High Copy Repeat Ty1 Elements
J. E. Chan (2011)
Microsatellite instability in yeast: dependence on repeat unit size and DNA mismatch repair genes.
E. Sia (1997)
Genomic deletions and point mutations induced in Saccharomyces cerevisiae by the trinucleotide repeats (GAA·TTC) associated with Friedreich's ataxia.
W. Tang (2013)
Recombination between retrotransposons as a source of chromosome rearrangements in the yeast Saccharomyces cerevisiae.
P. Mieczkowski (2006)
Evolutionary breakpoints are co-localized with fragile sites and intrachromosomal telomeric sequences in primates
A. Ruiz-Herrera (2004)
TLC1: template RNA component of Saccharomyces cerevisiae telomerase.
M. S. Singer (1994)
Expansion and length-dependent fragility of CTG repeats in yeast.
C. Freudenreich (1998)
Identification of a Ty insertion within the coding sequence of the S. cerevisiae URA3 gene
M. Rose (2004)
Everything you ever wanted to know about Saccharomyces cerevisiae telomeres: Beginning to end. Genetics 191(4):1073–1105
RJ Wellinger (2012)
Telomeres and mechanisms of Robertsonian fusion
P. Slijepcevic (1998)
Patching broken chromosomes with extranuclear cellular DNA.
X. Yu (1999)
Mutations arising during repair of chromosome breaks.
A. Malkova (2012)
Telomeric repeats far from the ends: mechanisms of origin and role in evolution
A. Ruiz-Herrera (2008)

This paper is referenced by
Chromatin dynamics of plant telomeres and ribosomal genes.
M. Dvořáčková (2015)
Mechanisms and Regulation of Mitotic Recombination in Saccharomyces cerevisiae
L. Symington (2014)
Crosstalk between telomere maintenance and radiation effects: A key player in the process of radiation-induced carcinogenesis.
G. Shim (2014)
The MLH1 ATPase domain is needed for suppressing aberrant formation of interstitial telomeric sequences.
Pingping Jia (2018)
Transposon-mediated telomere destabilization: a driver of genome evolution in the blast fungus
M. Rahnama (2020)
Telomeric small RNAs in the genus Caenorhabditis.
Stephen Frenk (2019)
Microhomology-mediated end joining induces hypermutagenesis at breakpoint junctions
S. Sinha (2017)
Interstitial Telomere Sequences Disrupt Break Induced Replication
E. Stivison (2019)
Repeat-driven generation of antigenic diversity in a major human pathogen Trypanosoma cruzi
Carlos Talavera-López (2018)
How to become a successful invasive tapeworm: a case study of abandoned sexuality and exceptional chromosome diversification in the triploid carp parasite Atractolytocestus huronensis Anthony, 1958 (Caryophyllidea: Lytocestidae)
M. Špakulová (2019)
Guidelines for DNA recombination and repair studies: Cellular assays of DNA repair pathways
H. Klein (2019)
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Anna Y. Aksenova ()
Genetic Control of Genomic Alterations Induced in Yeast by Interstitial Telomeric Sequences
A. moore (2018)
CNV instability associated with DNA replication dynamics: evidence for replicative mechanisms in CNV mutagenesis.
Ling-Ling Chen (2015)
Nanopore sequencing of complex genomic rearrangements in yeast reveals mechanisms of repeat-mediated double-strand break repair.
Ryan J. McGinty (2017)
DNA Instability Maintains the Repeat Length of the Yeast RNA Polymerase II C-terminal Domain*
Summer A Morrill (2016)
Interstitial telomeric repeats-associated DNA breaks
O. Shubernetskaya (2017)
The yeast core spliceosome maintains genome integrity through R-loop prevention and α-tubulin expression
Annie S. Tam (2018)
Telomere Capping Protein Stn1p Require the RAD6-Mediated Ubiquitination Pathway for DNA Repair and Function in Global DNA Replication
Tim Q. Tran (2016)
Ubiquitin C-terminal hydrolase isozyme L1 is associated with shelterin complex at interstitial telomeric sites
Aleksandar Ilic (2017)
Characterization of long G4-rich enhancer-associated genomic regions engaging in a novel loop:loop ‘G4 Kissing’ interaction
Jonathan D. Williams (2020)
Pathways and Mechanisms that Prevent Genome Instability in Saccharomyces cerevisiae
C. Putnam (2017)
Stochastic gene expression, phenotypic variability and adaptation of budding yeast to environmental stresses
J. Liu (2015)
Elevated Genome-Wide Instability in Yeast Mutants Lacking RNase H Activity
K. O’Connell (2015)
Cis- and Trans-Modifiers of Repeat Expansions: Blending Model Systems with Human Genetics.
Ryan J. McGinty (2018)
Comparative cytogenetics of tree frogs of the Dendropsophus marmoratus (Laurenti, 1768) group: conserved karyotypes and interstitial telomeric sequences
L. R. Teixeira (2016)
Asymmetric Processing of DNA Ends at a Double-Strand Break Leads to Unconstrained Dynamics and Ectopic Translocation.
Isabella Marcomini (2018)
Ku Binding on Telomeres Occurs at Sites Distal from the Physical Chromosome Ends
Mélanie V Larcher (2016)
Topoisomerase 2 Is Dispensable for the Replication and Segregation of Small Yeast Artificial Chromosomes (YACs)
Jorge Cebrián (2014)
Transposon-mediated telomere destabilization: a driver of genome evolution in the blast fungus
Mostafa Rahnama (2019)
Expansion of Interstitial Telomeric Sequences in Yeast.
Anna Y. Aksenova (2015)
Centromere deletion in Cryptococcus deuterogattii leads to neocentromere formation and chromosome fusions
Klaas Schotanus (2019)
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