Online citations, reference lists, and bibliographies.
← Back to Search

Low Levels Of DNA Polymerase Alpha Induce Mitotic And Meiotic Instability In The Ribosomal DNA Gene Cluster Of Saccharomyces Cerevisiae

A. M. Casper, P. Mieczkowski, M. Gawel, T. Petes
Published 2008 · Medicine, Biology

Cite This
Download PDF
Analyze on Scholarcy
Share
The ribosomal DNA (rDNA) genes of Saccharomyces cerevisiae are located in a tandem array of about 150 repeats. Using a diploid with markers flanking and within the rDNA array, we showed that low levels of DNA polymerase alpha elevate recombination between both homologues and sister chromatids, about five-fold in mitotic cells and 30-fold in meiotic cells. This stimulation is independent of Fob1p, a protein required for the programmed replication fork block (RFB) in the rDNA. We observed that the fob1 mutation alone significantly increased meiotic, but not mitotic, rDNA recombination, suggesting a meiosis-specific role for this protein. We found that meiotic cells with low polymerase alpha had decreased Sir2p binding and increased Spo11p-catalyzed double-strand DNA breaks in the rDNA. Furthermore, meiotic crossover interference in the rDNA is absent. These results suggest that the hyper-Rec phenotypes resulting from low levels of DNA polymerase alpha in mitosis and meiosis reflect two fundamentally different mechanisms: the increased mitotic recombination is likely due to increased double-strand DNA breaks (DSBs) resulting from Fob1p-independent stalled replication forks, whereas the hyper-Rec meiotic phenotype results from increased levels of Spo11-catalyzed DSBs in the rDNA.
This paper references
Genomic instability induced by mutations in Saccharomyces cerevisiae POL1.
P. J. Gutiérrez (2003)
10.1038/ncb1619
The Smc5–Smc6 complex and SUMO modification of Rad52 regulates recombinational repair at the ribosomal gene locus
Jordi Torres-Rosell (2007)
10.1101/GAD.1108403
Association of the RENT complex with nontranscribed and coding regions of rDNA and a regional requirement for the replication fork block protein Fob1 in rDNA silencing.
J. Huang (2003)
Inaugural Article: Global mapping of meiotic recombination hotspots and coldspots in the yeast Saccharomyces cerevisiae
J. Gerton (2000)
10.1074/JBC.M301610200
Dna2 Helicase/Nuclease Causes Replicative Fork Stalling and Double-strand Breaks in the Ribosomal DNA of Saccharomyces cerevisiae*
Tao Weitao (2003)
10.1002/j.1460-2075.1996.tb00517.x
Gene conversion plays the major role in controlling the stability of large tandem repeats in yeast.
S. Gangloff (1996)
10.1016/S0092-8674(00)80741-2
Pch2 Links Chromatin Silencing to Meiotic Checkpoint Control
P. San-Segundo (1999)
10.1016/J.CEB.2005.09.003
The DNA damage response during DNA replication.
D. Branzei (2005)
10.1128/MMBR.63.2.349-404.1999
Multiple Pathways of Recombination Induced by Double-Strand Breaks in Saccharomyces cerevisiae
F. Pâques (1999)
10.1016/S0092-8674(04)00414-3
SIR2 Regulates Recombination between Different rDNA Repeats, but Not Recombination within Individual rRNA Genes in Yeast
T. Kobayashi (2004)
10.1101/GAD.1478906
The S. cerevisiae Rrm3p DNA helicase moves with the replication fork and affects replication of all yeast chromosomes.
A. Azvolinsky (2006)
Organization of the yeast ribosomal RNA gene cluster via cloning and restriction analysis.
K. Nath (1977)
10.1016/J.MRFMMM.2003.08.015
Evidence that yeast SGS1, DNA2, SRS2, and FOB1 interact to maintain rDNA stability.
Tao Weitao (2003)
10.1101/GAD.12.24.3821
Expansion and contraction of ribosomal DNA repeats in Saccharomyces cerevisiae: requirement of replication fork blocking (Fob1) protein and the role of RNA polymerase I.
T. Kobayashi (1998)
10.1073/pnas.0700412104
Loss of a histone deacetylase dramatically alters the genomic distribution of Spo11p-catalyzed DNA breaks in Saccharomyces cerevisiae
P. Mieczkowski (2007)
[Eukaryotic DNA polymerases].
A. Czechowska (2005)
10.1016/J.DNAREP.2007.02.004
Maintenance of fork integrity at damaged DNA and natural pause sites.
H. Tourrière (2007)
10.1128/MCB.8.11.4927
Organization of replication of ribosomal DNA in Saccharomyces cerevisiae.
M. Linskens (1988)
The Analysis of Tetrad Data.
H. Papazian (1952)
Segregation of recombinant chromatids following mitotic crossing over in yeast.
P. Chua (1991)
10.1016/S0092-8674(04)00249-1
Imposition of Crossover Interference through the Nonrandom Distribution of Synapsis Initiation Complexes
J. Fung (2004)
10.1016/0092-8674(89)90681-8
A new role for a yeast transcriptional silencer gene, SIR2, in regulation of recombination in ribosomal DNA
S. Gottlieb (1989)
10.1016/0092-8674(88)90222-X
A replication fork barrier at the 3′ end of yeast ribosomal RNA genes
B. Brewer (1988)
10.1016/s0076-6879(00)x0276-5
Guide to yeast genetics and molecular biology.
J. Maier (1991)
10.1046/j.1356-9597.2001.00508.x
Replication fork block protein, Fob1, acts as an rDNA region specific recombinator in S. cerevisiae
K. Johzuka (2002)
10.1093/emboj/cdg180
The yeast Sgs1 helicase is differentially required for genomic and ribosomal DNA replication
Gwennaelle Versini (2003)
10.1016/S0092-8674(00)80316-5
Holliday Junctions Accumulate in Replication Mutants via a RecA Homolog-Independent Mechanism
H. Zou (1997)
10.1016/J.BIOCHI.2004.10.020
Checkpoint responses to replication fork barriers.
S. Lambert (2005)
10.1016/S0092-8674(80)80052-3
Unequal meiotic recombination within tandem arrays of yeast ribosomal DNA genes
T. Petes (1980)
10.1007/s00294-002-0319-6
Role of SGS1 and SLX4 in maintaining rDNA structure in Saccharomyces cerevisiae
V. Kaliraman (2002)
10.1073/pnas.0605778103
Selection and analysis of spontaneous reciprocal mitotic cross-overs in Saccharomyces cerevisiae
M. A. Barbera (2006)
10.1016/S0300-9084(00)00344-8
Mechanisms and consequences of replication fork arrest.
O. Hyrien (2000)
Analysis of meiotic recombination pathways in the yeast Saccharomyces cerevisiae.
Y. Mao-Draayer (1996)
10.1073/PNAS.74.11.5091
Simple Mendelian inheritance of the reiterated ribosomal DNA of yeast.
T. Petes (1977)
10.1128/MCB.23.24.9178-9188.2003
The Replication Fork Barrier Site Forms a Unique Structure with Fob1p and Inhibits the Replication Fork
T. Kobayashi (2003)
10.1101/GAD.1472706
Inhibition of homologous recombination by a cohesin-associated clamp complex recruited to the rDNA recombination enhancer.
J. Huang (2006)
10.1128/JB.138.1.185-192.1979
Meiotic mapping of yeast ribosomal deoxyribonucleic acid on chromosome XII.
T. Petes (1979)
10.1101/GAD.14.1.1
Replication fork pausing and recombination or "gimme a break".
R. Rothstein (2000)
10.1073/PNAS.72.12.5056
Electron microscopic observations on the meiotic karyotype of diploid and tetraploid Saccharomyces cerevisiae.
B. Byers (1975)
10.1093/NAR/12.18.7199
Correlation between suppressed meiotic recombination and the lack of DNA strand-breaks in the rRNA genes of Saccharomyces cerevisiae.
A. Høgset (1984)
10.1128/MCB.24.21.9568-9579.2004
A Coordinated Temporal Interplay of Nucleosome Reorganization Factor, Sister Chromatin Cohesion Factor, and DNA Polymerase α Facilitates DNA Replication
Y. Zhou (2004)
Biochemical Mutants in the Smut Fungus Ustilago Maydis.
D. Perkins (1949)
10.1016/j.cell.2004.12.039
Chromosomal Translocations in Yeast Induced by Low Levels of DNA Polymerase A Model for Chromosome Fragile Sites
Francene J. Lemoine (2005)
10.1038/nrm951
Recombinational repair and restart of damaged replication forks
P. McGlynn (2002)
10.1016/S1097-2765(00)80472-4
Elimination of replication block protein Fob1 extends the life span of yeast mother cells.
P. Defossez (1999)
10.1353/SHO.0.0371
Gimme a Break!
B. Friedlander (2009)
10.1128/JB.134.1.295-305.1978
Characterization of two types of yeast ribosomal DNA genes.
T. Petes (1978)
10.1371/JOURNAL.PGEN.0020184
Recombination Hotspots Flank the Cryptococcus Mating-Type Locus: Implications for the Evolution of a Fungal Sex Chromosome
Yen-Ping Hsueh (2006)
10.2307/3760517
Guide to yeast genetics and molecular biology
C. Guthrie (1993)
10.1016/S0092-8674(04)00292-2
Crossover/Noncrossover Differentiation, Synaptonemal Complex Formation, and Regulatory Surveillance at the Leptotene/Zygotene Transition of Meiosis
G. Boerner (2004)
10.1534/GENETICS.104.027961
Gene Conversion and Crossing Over Along the 405-kb Left Arm of Saccharomyces cerevisiae Chromosome VII
A. Malkova (2004)
10.1534/genetics.108.086918
On the “NPD Ratio” as a Test for Crossover Interference
F. Stahl (2008)
10.1016/S1097-2765(02)00508-7
Only connect: linking meiotic DNA replication to chromosome dynamics.
S. Forsburg (2002)
10.1146/ANNUREV.GE.05.120171.001251
Recombination in yeast.
S. Fogel (1971)
10.1101/GAD.1154704
Local chromatin structure at the ribosomal DNA causes replication fork pausing and genome instability in the absence of the S. cerevisiae DNA helicase Rrm3p.
J. Torres (2004)
10.1016/S0092-8674(04)00297-1
Early Decision Meiotic Crossover Interference prior to Stable Strand Exchange and Synapsis
D. Bishop (2004)
10.1128/MCB.20.20.7490-7504.2000
Increased Rates of Genomic Deletions Generated by Mutations in the Yeast Gene Encoding DNA Polymerase δ or by Decreases in the Cellular Levels of DNA Polymerase δ
R. Kokoska (2000)
10.1016/S0070-2153(01)52008-6
Mechanism and control of meiotic recombination initiation.
S. Keeney (2001)
10.1038/284426A0
Unequal crossing over in the ribosomal DNA of Saccharomyces cerevisiae
J. Szostak (1980)
10.1101/GAD.1085403
Transcription-dependent recombination and the role of fork collision in yeast rDNA.
Y. Takeuchi (2003)



This paper is referenced by
10.3390/genes9110539
Genome Instability Induced by Low Levels of Replicative DNA Polymerases in Yeast
Dao-Qiong Zheng (2018)
10.4061/2011/692301
Cancer, Senescence, and Aging: Translation from Basic Research to Clinics
M. LLeonart (2011)
10.1371/journal.pgen.1002015
Replicative Age Induces Mitotic Recombination in the Ribosomal RNA Gene Cluster of Saccharomyces cerevisiae
D. Lindstrom (2011)
10.4161/cc.9.16.12673
Eco1 is important for DNA damage repair in S. cerevisiae
S. Lu (2010)
CHARACTERIZATION OF THE COHESIN ACETYLTRANSFERASE ECO1 AND ITS ROLE IN NUCLEAR FUNCTIONS
S. Lu (2013)
10.1073/pnas.1406847111
Genome-wide high-resolution mapping of chromosome fragile sites in Saccharomyces cerevisiae
Wei Song (2014)
Mitotic Recombination in Saccharomyces cerevisiae Results from Genetic Instability at Fragile Site FS2
Shaylynn Miller (2015)
Computational discovery and analysis of rDNA sequence heterogeneity in yeast
C. West (2013)
10.1016/j.semcancer.2010.10.009
DNA replication fidelity and cancer.
Bradley D. Preston (2010)
10.1007/s00709-009-0051-x
Visualization by atomic force microscopy and FISH of the 45S rDNA gaps in mitotic chromosomes of Lolium perenne
J. Huang (2009)
10.1007/s13238-015-0134-8
Essential role of the iron-sulfur cluster binding domain of the primase regulatory subunit Pri2 in DNA replication initiation
L. Liu (2015)
10.1371/journal.pgen.1005098
Genome-Destabilizing Effects Associated with Top1 Loss or Accumulation of Top1 Cleavage Complexes in Yeast
S. L. Andersen (2015)
10.1371/journal.pgen.1003894
Genome-Wide High-Resolution Mapping of UV-Induced Mitotic Recombination Events in Saccharomyces cerevisiae
Yi Yin (2013)
10.1371/journal.pgen.1003817
Fragile Site Instability in Saccharomyces cerevisiae Causes Loss of Heterozygosity by Mitotic Crossovers and Break-Induced Replication
Danielle M. Rosen (2013)
10.1007/978-94-007-2561-4
Aging Research in Yeast
M. Breitenbach (2012)
10.4061/2011/103253
Self-Renewal Signalling in Presenescent Tetraploid IMR90 Cells
A. Huna (2011)
10.1007/978-94-007-2561-4_9
DNA damage and DNA replication stress in yeast models of aging.
W. Burhans (2012)
10.1534/g3.118.200446
A Case Study of Genomic Instability in an Industrial Strain of Saccharomyces cerevisiae
Aline Rodrigues-Prause (2018)
Regulation of stability and copy number of tandem repeats in Saccharomyces cerevisiae
Devika Salim (2020)
10.1073/pnas.1107390109
Transgene-mediated cosuppression and RNA interference enhance germ-line apoptosis in Caenorhabditis elegans
A. Adamo (2012)
10.1371/journal.pgen.1007006
DNA replication stress restricts ribosomal DNA copy number
Devika Salim (2017)
10.1534/g3.111.000554
Replication Stress-Induced Chromosome Breakage Is Correlated with Replication Fork Progression and Is Preceded by Single-Stranded DNA Formation
W. Feng (2011)
Study of the Structure-Related Functions of Eukaryotic Primase-POL ALPHA Complex During Replication
Yinbo Zhang (2016)
10.5772/18142
Function of DNA Polymerase α in a Replication Fork and its Putative Roles in Genomic Stability and Eukaryotic Evolution
M. Takemura (2011)
10.1371/journal.pgen.1008430
The effects of manipulating levels of replication initiation factors on origin firing efficiency in yeast
K. L. Lynch (2019)
10.1534/genetics.111.138180
Haploidization in Saccharomyces cerevisiae Induced by a Deficiency in Homologous Recombination
Wei Song (2012)
10.1038/ng.2678
Massive genomic variation and strong selection in Arabidopsis thaliana lines from Sweden
Quan Long (2013)
Semantic Scholar Logo Some data provided by SemanticScholar