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

Replication Stress-Induced Chromosome Breakage Is Correlated With Replication Fork Progression And Is Preceded By Single-Stranded DNA Formation

W. Feng, Sara C. Di Rienzi, M. Raghuraman, B. Brewer
Published 2011 · Medicine, Biology

Cite This
Download PDF
Analyze on Scholarcy
Share
Chromosome breakage as a result of replication stress has been hypothesized to be the direct consequence of defective replication fork progression, or “collapsed” replication forks. However, direct and genome-wide evidence that collapsed replication forks give rise to chromosome breakage is still lacking. Previously we showed that a yeast replication checkpoint mutant mec1-1, after transient exposure to replication impediment imposed by hydroxyurea (HU), failed to complete DNA replication, accumulated single-stranded DNA (ssDNA) at the replication forks, and fragmented its chromosomes. In this study, by following replication fork progression genome-wide via ssDNA detection and by direct mapping of chromosome breakage after HU exposure, we have tested the hypothesis that the chromosome breakage in mec1 cells occurs at collapsed replication forks. We demonstrate that sites of chromosome breakage indeed correlate with replication fork locations. Moreover, ssDNA can be detected prior to chromosome breakage, suggesting that ssDNA accumulation is the common precursor to double strand breaks at collapsed replication forks.
This paper references
10.1038/nsmb.1754
Systematic identification of fragile sites via genome-wide location analysis of γ-H2AX
R. Szilard (2010)
10.1534/genetics.109.106385
Chromosome Aberrations Resulting From Double-Strand DNA Breaks at a Naturally Occurring Yeast Fragile Site Composed of Inverted Ty Elements Are Independent of Mre11p and Sae2p
A. M. Casper (2009)
10.1038/ncb1358
Genomic mapping of single-stranded DNA in hydroxyurea-challenged yeasts identifies origins of replication
W. Feng (2006)
10.1128/MCB.02063-06
Genome-Wide Redistribution of Meiotic Double-Strand Breaks in Saccharomyces cerevisiae
Nicolas Robine (2006)
10.1126/SCIENCE.1071398
ATR Homolog Mec1 Promotes Fork Progression, Thus Averting Breaks in Replication Slow Zones
R. Cha (2002)
10.1534/genetics.109.107508
Centromere Replication Timing Determines Different Forms of Genomic Instability in Saccharomyces cerevisiae Checkpoint Mutants During Replication Stress
W. Feng (2009)
10.1016/j.cub.2007.10.066
Mapping of Meiotic Single-Stranded DNA Reveals Double-Strand-Break Hotspots near Centromeres and Telomeres
Hannah G. Blitzblau (2007)
10.1016/j.cell.2011.02.009
A Hierarchical Combination of Factors Shapes the Genome-wide Topography of Yeast Meiotic Recombination Initiation
J. Pan (2011)
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)
Heritable fragile sites on human chromosomes II. Distribution, phenotypic effects, and cytogenetics.
G. Sutherland (1979)
Heritable fragile sites on human chromosomes II. Distribution, phenotypic effects, and cytogenetics.
Sutherland Gr (1979)
10.1016/J.MOLCEL.2004.11.032
Exo1 processes stalled replication forks and counteracts fork reversal in checkpoint-defective cells.
Cecilia Cotta-Ramusino (2005)
10.1016/S1097-2765(01)00216-7
An origin-deficient yeast artificial chromosome triggers a cell cycle checkpoint.
A. J. van Brabant (2001)
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)
10.1128/MCB.14.12.8229
Transposition of the yeast retroviruslike element Ty3 is dependent on the cell cycle.
Thomas M. Menees (1994)
10.1101/GAD.1392506
Cycles of chromosome instability are associated with a fragile site and are increased by defects in DNA replication and checkpoint controls in yeast.
A. Admire (2006)
10.1371/journal.pgen.1000105
Low Levels of DNA Polymerase Alpha Induce Mitotic and Meiotic Instability in the Ribosomal DNA Gene Cluster of Saccharomyces cerevisiae
A. M. Casper (2008)
10.1158/0008-5472.CAN-04-1433
Radiation Sensitivity, H2AX Phosphorylation, and Kinetics of Repair of DNA Strand Breaks in Irradiated Cervical Cancer Cell Lines
J. Banáth (2004)
10.1038/sj.emboj.7601251
Genome‐wide replication profiles of S‐phase checkpoint mutants reveal fragile sites in yeast
Miruthubashini Raveendranathan (2006)



This paper is referenced by
Mitotic Recombination in Saccharomyces cerevisiae Results from Genetic Instability at Fragile Site FS2
Shaylynn Miller (2015)
10.1038/ncomms7154
Macrotene chromosomes provide insights to a new mechanism of high-order gene amplification in eukaryotes
A. Thierry (2015)
10.3390/biom5032123
Managing Single-Stranded DNA during Replication Stress in Fission Yeast
S. Sabatinos (2015)
10.1073/pnas.1406847111
Genome-wide high-resolution mapping of chromosome fragile sites in Saccharomyces cerevisiae
Wei Song (2014)
10.3389/fgene.2013.00026
The DNA damage checkpoint response to replication stress: A Game of Forks
Rachel Jossen (2013)
10.14232/phd.2054
Def1 promotes polymerase exchange at stalled replication forks upon DNA damage
Daraba Andreea (2014)
10.1073/pnas.1319313110
Genome rearrangements caused by interstitial telomeric sequences in yeast
Anna Y Aksenova (2013)
10.3390/cells3020592
The Cytolethal Distending Toxin Effects on Mammalian Cells: A DNA Damage Perspective
Elisabeth Bezine (2014)
10.1080/15384101.2015.1127478
ARTIK-52 induces replication-dependent DNA damage and p53 activation exclusively in cells of prostate and breast cancer origin
Daria Fleyshman (2016)
10.1371/journal.pgen.1003931
Recombinogenic Conditions Influence Partner Choice in Spontaneous Mitotic Recombination
J. Cauwood (2013)
10.1101/gr.224527.117
The organization of genome duplication is a critical determinant of the landscape of genome maintenance.
Blanca Gómez-Escoda (2018)
10.1146/annurev-genom-091416-035314
Recent Advancements in DNA Damage-Transcription Crosstalk and High-Resolution Mapping of DNA Breaks.
V. Vitelli (2017)
10.1091/mbc.E19-03-0156
Inhibition of spindle extension through the yeast S phase checkpoint is coupled to replication fork stability and the integrity of centromeric DNA
J. Julius (2019)
10.1007/978-1-4939-0888-2
Cell Cycle Control
E. Noguchi (2014)
10.1128/JVI.03650-14
Viral DNA Replication-Dependent DNA Damage Response Activation during BK Polyomavirus Infection
Brandy Verhalen (2015)
10.1128/MCB.01060-12
Continued DNA Synthesis in Replication Checkpoint Mutants Leads to Fork Collapse
S. Sabatinos (2012)
10.1111/cmi.12028
From single‐strand breaks to double‐strand breaks during S‐phase: a new mode of action of the Escherichia coli Cytolethal Distending Toxin
Y. Fedor (2013)
10.3390/genes8010010
Mec1/ATR, the Program Manager of Nucleic Acids Inc.
Wenyi Feng (2016)
10.1101/384644
The limiting DNA replication initiation factors Sld2 and Sld3 influence origin efficiency independent of origin firing time
Kelsey L Lynch (2018)
10.1371/journal.pgen.1002978
Topoisomerase II– and Condensin-Dependent Breakage of MEC1ATR-Sensitive Fragile Sites Occurs Independently of Spindle Tension, Anaphase, or Cytokinesis
Nadia Hashash (2012)
10.1111/febs.15568
Exploring the SSBreakome: genome-wide mapping of DNA single-strand breaks by next-generation sequencing.
N. Zilio (2020)
10.1016/j.molcel.2015.10.023
Essential Roles of the Smc5/6 Complex in Replication through Natural Pausing Sites and Endogenous DNA Damage Tolerance
Demis Menolfi (2015)
10.5772/51393
Preserving the Replication Fork in Response to Nucleotide Starvation: Evading the Replication Fork Collapse Point
S. Sabatinos (2013)
10.1371/journal.pgen.1006479
Ku Binding on Telomeres Occurs at Sites Distal from the Physical Chromosome Ends
Mélanie V Larcher (2016)
10.1371/journal.pbio.2005542
Decoding the chromatin proteome of a single genomic locus by DNA sequencing
T. Korthout (2018)
10.1083/jcb.201209002
FBH1 promotes DNA double-strand breakage and apoptosis in response to DNA replication stress
Yeon-Tae Jeong (2013)
10.1007/978-1-4939-0888-2_27
Analysis of ssDNA gaps and DSBs in genetically unstable yeast cultures.
Jie Peng (2014)
Decrypting chromatin states: DNA barcoding technologies to study chromatin interactions
T. Korthout (2019)
10.1002/bies.201400052
Unique features of DNA replication in mitochondria: A functional and evolutionary perspective
I. Holt (2014)
Proteomics of spindle checkpoint complexes and characterisation of novel interactors
Sjaak van der Sar (2014)
10.1101/gr.146357.112
Mapping genomic hotspots of DNA damage by a single-strand-DNA-compatible and strand-specific ChIP-seq method.
Zhi-Xiong Zhou (2013)
10.1093/toxsci/kft069
Hydroxyurea Exposure Triggers Tissue-Specific Activation of p38 Mitogen-Activated Protein Kinase Signaling and the DNA Damage Response in Organogenesis-Stage Mouse Embryos
Serena Banh (2013)
See more
Semantic Scholar Logo Some data provided by SemanticScholar