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

Mapping Of Meiotic Single-Stranded DNA Reveals Double-Strand-Break Hotspots Near Centromeres And Telomeres

Hannah G. Blitzblau, G. Bell, Joseph Rodriguez, S. P. Bell, Andreas Hochwagen
Published 2007 · Biology, Medicine

Cite This
Download PDF
Analyze on Scholarcy
Share
BACKGROUND Every chromosome requires at least one crossover to be faithfully segregated during meiosis. At least two levels of regulation govern crossover distribution: where the initiating DNA double-strand breaks (DSBs) occur and whether those DSBs are repaired as crossovers. RESULTS We mapped meiotic DSBs in budding yeast by identifying sites of DSB-associated single-stranded DNA (ssDNA) accumulation. These analyses revealed substantial DSB activity in pericentrometric regions, in which crossover formation is largely absent. Our data suggest that centromeric suppression of recombination occurs at the level of break repair rather than DSB formation. Additionally, we found an enrichment of DSBs within a approximately 100 kb region near the ends of all chromosomes. Introduction of new telomeres was sufficient for inducing large ectopic regions of increased DSB formation, thereby revealing a remarkable long-range effect of telomeres on DSB formation. The concentration of DSBs close to chromosome ends increases the relative DSB density on small chromosomes, providing an interference-independent mechanism that ensures that all chromosomes receive at least one crossover per homolog pair. CONCLUSIONS Together, our results indicate that selective DSB repair accounts for crossover suppression near centromeres and suggest a simple telomere-guided mechanism that ensures sufficient DSB activity on all chromosomes.
This paper references
Meiosis-induced doublestrand break sites determined by yeast chromatin
T. C. Wu (1994)
10.1038/35072078
Meiotic recombination hot spots and cold spots
Td. Petes (2001)
Meiotic sister chromatid recombination.
T. Petes (1995)
10.1016/0092-8674(94)90197-X
Crossover interference is abolished in the absence of a synaptonemal complex protein
M. Sym (1994)
10.1016/S0092-8674(01)80009-X
Components and Dynamics of DNA Replication Complexes in S. cerevisiae: Redistribution of MCM Proteins and Cdc45p during S Phase
O. Aparicio (1997)
10.1073/PNAS.95.1.247
Assaying genome-wide recombination and centromere functions with Arabidopsis tetrads.
G. Copenhaver (1998)
10.1083/JCB.151.1.95
Meiotic Telomere Protein Ndj1p Is Required for Meiosis-Specific Telomere Distribution, Bouquet Formation and Efficient Homologue Pairing
E. Trelles-Sticken (2000)
10.1016/j.cell.2004.08.008
Modifying Histones and Initiating Meiotic Recombination New Answers to an Old Question
S. Maleki (2004)
10.1016/S1097-2765(04)00034-6
Association of Mre11p with double-strand break sites during yeast meiosis.
V. Borde (2004)
10.1016/S0092-8674(00)80378-5
Interhomolog Bias during Meiotic Recombination: Meiotic Functions Promote a Highly Differentiated Interhomolog-Only Pathway
Anthony Schwacha (1997)
10.1159/000086896
Effect of meiotic recombination on the production of aneuploid gametes in humans
N. Lamb (2005)
10.1126/SCIENCE.290.5492.806
Direct coupling between meiotic DNA replication and recombination initiation.
V. Borde (2000)
10.1128/MCB.26.3.1014-1027.2006
Global Analysis of the Relationship between the Binding of the Bas1p Transcription Factor and Meiosis-Specific Double-Strand DNA Breaks in Saccharomyces cerevisiae
P. Mieczkowski (2006)
10.1038/35085086
A bouquet makes ends meet
H. Scherthan (2001)
A function for subtelomeric DNA in Saccharomyces cerevisiae.
A. Barton (2003)
10.1534/GENETICS.104.027789
Does Crossover Interference Count in Saccharomyces cerevisiae?
F. Stahl (2004)
10.1016/S0092-8674(01)00416-0
Differential Timing and Control of Noncrossover and Crossover Recombination during Meiosis
T. Allers (2001)
10.1016/0092-8674(92)90446-J
DMC1: A meiosis-specific yeast homolog of E. coli recA required for recombination, synaptonemal complex formation, and cell cycle progression
D. Bishop (1992)
10.2144/05386RR01
PCR-mediated repeated chromosome splitting in Saccharomyces cerevisiae.
M. Sugiyama (2005)
10.1016/S0092-8674(02)01167-4
Physical and Functional Interactions among Basic Chromosome Organizational Features Govern Early Steps of Meiotic Chiasma Formation
Y. Blat (2002)
Data Additional Experimental Procedures, four figures, and two tables are available at http://www.current-biology.com/cgi/content/full
(2003)
DMC 1 : A meiosis - specific yeast homolog of E . coli recA required for recombination , synaptonemal complex formation , and
D. K. Bishop (1992)
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)
10.1073/PNAS.74.11.5091
Simple Mendelian inheritance of the reiterated ribosomal DNA of yeast.
T. Petes (1977)
10.1101/GAD.14.4.493
Progression of meiotic DNA replication is modulated by interchromosomal interaction proteins, negatively by Spo11p and positively by Rec8p.
R. Cha (2000)
10.1038/ng917
A high-resolution recombination map of the human genome
A. Kong (2002)
10.1016/S0092-8674(01)00430-5
The Single-End Invasion An Asymmetric Intermediate at the Double-Strand Break to Double-Holliday Junction Transition of Meiotic Recombination
N. Hunter (2001)
10.1534/GENETICS.104.033555
Does Chromosome Size Affect Map Distance and Genetic Interference in Budding Yeast?
Dana Turney (2004)
Klein for providing strains. We thank J. Falk for technical assistance and M. de Vries, A. Amon, and T. Orr-Weaver for helpful discussions and critical reading of the manuscript. We are indebted to
Acknowledgments We
DMC1 functions in a Saccharomyces cerevisiae meiotic pathway that is largely independent of the RAD51 pathway.
M. Dresser (1997)
10.1126/SCIENCE.276.5316.1252
Ndj1p, a meiotic telomere protein required for normal chromosome synapsis and segregation in yeast.
M. N. Conrad (1997)
10.1016/j.cell.2005.06.026
Genome-wide Map of Nucleosome Acetylation and Methylation in Yeast
D. K. Pokholok (2005)
10.1016/S0092-8674(03)00083-7
Un Ménage à Quatre The Molecular Biology of Chromosome Segregation in Meiosis
Mark Petronczki (2003)
10.1007/s004120000098
Decreased meiotic reciprocal recombination in subtelomeric regions in Saccharomyces cerevisiae
Y. Su (2000)
10.1128/MCB.02063-06
Genome-Wide Redistribution of Meiotic Double-Strand Breaks in Saccharomyces cerevisiae
Nicolas Robine (2006)
is an investigator of the Howard Hughes Medical Institute. Received: July 31
(2007)
10.1016/j.cell.2005.07.010
The FK506 Binding Protein Fpr3 Counteracts Protein Phosphatase 1 to Maintain Meiotic Recombination Checkpoint Activity
Andreas Hochwagen (2005)
10.1016/S0092-8674(04)00297-1
Early Decision Meiotic Crossover Interference prior to Stable Strand Exchange and Synapsis
D. Bishop (2004)
10.1038/386414A0
An atypical topoisomerase II from archaea with implications for meiotic recombination
A. Bergerat (1997)
10.1093/OXFORDJOURNALS.MOLBEV.A004176
Integrating genomics, bioinformatics, and classical genetics to study the effects of recombination on genome evolution.
John A. Birdsell (2002)
10.1016/0092-8674(93)90114-6
ZIP1 is a synaptonemal complex protein required for meiotic chromosome synapsis
M. Sym (1993)
10.1534/genetics.106.058933
Centromere-Proximal Crossovers Are Associated With Precocious Separation of Sister Chromatids During Meiosis in Saccharomyces cerevisiae
B. Rockmill (2006)
10.1016/0092-8674(90)90072-M
A pathway for generation and processing of double-strand breaks during meiotic recombination in S. cerevisiae
L. Cao (1990)
10.1073/PNAS.94.10.5213
Clustering of meiotic double-strand breaks on yeast chromosome III.
F. Baudat (1997)
cycle progression
C. Buhler (2007)
Inaugural Article: Global mapping of meiotic recombination hotspots and coldspots in the yeast Saccharomyces cerevisiae
J. Gerton (2000)
10.1007/s00412-006-0048-6
From early homologue recognition to synaptonemal complex formation
D. Zickler (2006)
Accession Numbers All data sets in this publication have been deposited in the NCBI Gene Expression Omnibus
10.1126/SCIENCE.1083634
Distinct Cohesin Complexes Organize Meiotic Chromosome Domains
Tomoya S. Kitajima (2003)
The in vivo replication origin of the yeast 2 microns plasmid.
J. Huberman (1987)
10.1016/S0065-2660(08)60330-2
2 Meiotic Sister Chromatid Recombination
T. Petes (1995)
10.1101/GAD.7.7A.1133
Silent domains are assembled continuously from the telomere and are defined by promoter distance and strength, and by SIR3 dosage.
H. Renauld (1993)
10.1073/PNAS.90.14.6621
Transcription factors are required for the meiotic recombination hotspot at the HIS4 locus in Saccharomyces cerevisiae.
M. White (1993)
10.1002/(SICI)1097-0061(199904)15:6<507::AID-YEA369>3.0.CO;2-P
Heterologous URA3MX cassettes for gene replacement in Saccharomyces cerevisiae
A. Goldstein (1999)
10.1146/ANNUREV.GE.05.120171.001251
Recombination in yeast.
S. Fogel (1971)
10.1016/0092-8674(87)90643-X
The in vivo replication origin of the yeast 2μm plasmid
J. Huberman (1987)
10.1016/0092-8674(88)90428-X
A yeast acts in (Cis) to inhibit meiotic gene conversion of adjacent sequences
E. Lambie (1988)
10.1126/SCIENCE.1566070
Chromosome size-dependent control of meiotic recombination.
D. Kaback (1992)
10.1016/S0092-8674(00)81876-0
Meiosis-Specific DNA Double-Strand Breaks Are Catalyzed by Spo11, a Member of a Widely Conserved Protein Family
S. Keeney (1997)
10.1016/0092-8674(91)90270-9
Extensive 3′-overhanging, single-stranded DNA associated with the meiosis-specific double-strand breaks at the ARG4 recombination initiation site
Hong Sun (1991)
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)
Meiotic and mitotic behavior of dicentric chromosomes in Saccharomyces cerevisiae.
J. Haber (1984)
10.1038/82539
The core meiotic transcriptome in budding yeasts
M. Primig (2000)
A yeast centromere acts in cis to inhibit meiotic gene conversion of adjacent sequences.
E. Lambie (1988)
10.1038/ncb1358
Genomic mapping of single-stranded DNA in hydroxyurea-challenged yeasts identifies origins of replication
W. Feng (2006)
10.1146/ANNUREV.GE.29.120195.002231
Meiotic recombination hotspots.
M. Lichten (1995)
10.1101/GAD.1373005
The core centromere and Sgo1 establish a 50-kb cohesin-protected domain around centromeres during meiosis I.
B. Kiburz (2005)
Extensive 30-overhanging, single-stranded DNA associated with the meiosis-specific double-strand breaks at the ARG4 recombination initiation
H. Sun (1991)
10.1073/PNAS.95.12.6739
The high mobility group protein Abf2p influences the level of yeast mitochondrial DNA recombination intermediates in vivo.
D. MacAlpine (1998)
10.1371/JOURNAL.PBIO.0050324
Mapping Meiotic Single-Strand DNA Reveals a New Landscape of DNA Double-Strand Breaks in Saccharomyces cerevisiae
Cyril Buhler (2007)
10.1101/GAD.11.14.1786
Tam1, a telomere-associated meiotic protein, functions in chromosome synapsis and crossover interference.
P. Chua (1997)
10.1093/NAR/30.4.E15
Normalization for cDNA microarray data: a robust composite method addressing single and multiple slide systematic variation.
Yee Hwa Yang (2002)
10.1126/SCIENCE.8290959
Meiosis-induced double-strand break sites determined by yeast chromatin structure.
T. Wu (1994)
10.1073/PNAS.92.18.8512
Crossover and noncrossover recombination during meiosis: timing and pathway relationships.
A. Storlazzi (1995)
10.1101/GAD.321105
The control of Spo11's interaction with meiotic recombination hotspots.
Silvia Prieler (2005)



This paper is referenced by
10.1038/nrm2849
Genome destabilization by homologous recombination in the germ line
M. Sasaki (2010)
10.1038/s41467-019-11232-7
m6A modification of a 3′ UTR site reduces RME1 mRNA levels to promote meiosis
G. G. Bushkin (2019)
10.1534/genetics.108.090142
Domain-Specific Regulation of Recombination in Caenorhabditis elegans in Response to Temperature, Age and Sex
Jaclyn G Y Lim (2008)
10.1534/genetics.107.083493
Meiotic Recombination at the Ends of Chromosomes in Saccharomyces cerevisiae
A. Barton (2008)
Primer Centromeres Convert but Don't Cross the Role of Crossing over in Meiosis
Paul B. Talbert ()
10.1016/j.tig.2010.02.003
Discrete DNA sites regulate global distribution of meiotic recombination.
W. Wahls (2010)
10.1534/genetics.111.129031
Pch2 Modulates Chromatid Partner Choice During Meiotic Double-Strand Break Repair in Saccharomyces cerevisiae
Sarah Zanders (2011)
10.1016/j.gene.2012.08.012
Ewing's sarcoma: analysis of single nucleotide polymorphism in the EWS gene.
D. S. B. S. Silva (2012)
10.1038/emboj.2008.257
Histone H3 lysine 4 trimethylation marks meiotic recombination initiation sites
V. Borde (2009)
10.1042/EBC20190076
Adaptations for centromere function in meiosis
Reinier Prosée (2020)
10.7554/eLife.10850
The kinetochore prevents centromere-proximal crossover recombination during meiosis
Nadine Vincenten (2015)
10.7554/eLife.07424
Transcription dynamically patterns the meiotic chromosome-axis interface
Xiaoji Sun (2015)
Mapping Genetic Interaction Networks in Yeast
Anastasija Baryshnikova (2013)
10.1007/7050_2008_040
Meiotic Chromatin: The Substrate for Recombination Initiation
M. Lichten (2008)
10.1101/2020.09.24.312371
Molecular mechanisms for environmentally induced plasticity in the positioning of meiotic recombination at hotspots
Tresor O. Mukiza (2020)
10.1371/journal.pgen.1003898
Inhibition of the Smc5/6 Complex during Meiosis Perturbs Joint Molecule Formation and Resolution without Significantly Changing Crossover or Non-crossover Levels
I. Lilienthal (2013)
INVESTIGATION OF CHROMOSOME SIZE EFFECT ON THE RATE OF CROSSOVERS IN THE MEIOTIC YEAST Saccharomyces cerevisiae
A Thesis (2014)
The evolution of recombination and genomic structures: a modeling approach
Alexandra Popa (2011)
10.1101/381137
Synthetic chromosome fusion: effects on genome structure and function
Jingchuan Luo (2018)
10.1101/064519
Local chromosome context is a major determinant of crossover pathway biochemistry during budding yeast meiosis
D. Medhi (2016)
10.1371/journal.pgen.1000533
Evolution of Mutational Robustness in the Yeast Genome: A Link to Essential Genes and Meiotic Recombination Hotspots
P. J. Keller (2009)
10.1371/journal.pone.0156817
Altered Crossover Distribution and Frequency in Spermatocytes of Infertile Men with Azoospermia
He Ren (2016)
10.1371/journal.pone.0029711
Analysis of Biological Features Associated with Meiotic Recombination Hot and Cold Spots in Saccharomyces cerevisiae
Loren Hansen (2011)
10.4161/cc.19733
Scale matters
Sam E. Tischfield (2012)
10.1371/journal.pgen.1000557
Pch2 Links Chromosome Axis Remodeling at Future Crossover Sites and Crossover Distribution during Yeast Meiosis
N. Joshi (2009)
10.1007/978-1-61779-129-1_3
Characterization of meiotic recombination initiation sites using pulsed-field gel electrophoresis.
S. Farmer (2011)
10.7554/eLife.00844
ATR/Mec1 prevents lethal meiotic recombination initiation on partially replicated chromosomes in budding yeast
Hannah G. Blitzblau (2013)
10.1534/genetics.112.145144
Chromosome Segregation in Budding Yeast: Sister Chromatid Cohesion and Related Mechanisms
A. Marston (2014)
10.1007/978-1-61779-129-1_4
Genome-wide detection of meiotic DNA double-strand break hotspots using single-stranded DNA.
Hannah G. Blitzblau (2011)
10.1371/journal.pgen.1002643
Separation of DNA Replication from the Assembly of Break-Competent Meiotic Chromosomes
Hannah G. Blitzblau (2012)
10.1093/gbe/evp033
Protein Rates of Evolution Are Predicted by Double-Strand Break Events, Independent of Crossing-over Rates
C. Weber (2009)
10.1101/2020.07.16.207068
DNA break formation induces Scc2/cohesin-dependent recruitment of condensin to meiotic chromosomes
Tovah E. Markowitz (2020)
See more
Semantic Scholar Logo Some data provided by SemanticScholar