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Preserving The Replication Fork In Response To Nucleotide Starvation: Evading The Replication Fork Collapse Point
S. Sabatinos, S. Forsburg
Published 2013 · Biology
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Replication fork progression is blocked by a variety impediments including DNA damage, aberrant DNA structures, or nucleotide depletion [1-3]. The response to replication fork stalling varies according the type of replication inhibition, the number of stalled forks and the duration of the treatment [3-7]. Stalled replication forks are at increased risk for DNA damage, which can lead to mutation or cell death [7-13]. The cell relies on the Intra-S phase checkpoint and DNA damage response proteins to preserve fork structure to allow recovery and resumption of the cell cycle [5, 10, 14-19]. Thus, the mechanisms that maintain replica‐ tion fork structure are crucial for genome maintenance, and form a primary barrier to malig‐ nant transformation [20, 21].
This paper references
Molecular anatomy and regulation of a stable replisome at a paused eukaryotic DNA replication fork.
A. Calzada (2005)
Checkpoint independence of most DNA replication origins in fission yeast
Katie L Mickle (2007)
Gross Chromosomal Rearrangements and Elevated Recombination at an Inducible Site-Specific Replication Fork Barrier
S. Lambert (2005)
The Interaction between Helicase and Primase Sets the Replication Fork Clock*
K. Tõugu (1996)
Replication Fork Arrest and rDNA Silencing Are Two Independent and Separable Functions of the Replication Terminator Protein Fob1 of Saccharomyces cerevisiae*
N. Bairwa (2010)
Hydroxyurea-Stalled Replication Forks Become Progressively Inactivated and Require Two Different RAD51-Mediated Pathways for Restart and Repair
E. Petermann (2010)
ATM is required for the cellular response to thymidine induced replication fork stress.
E. Bolderson (2004)
Posttranslational modifications of repair factors and histones in the cellular response to stalled replication forks.
Thomas Schleker (2009)
The Human Tim/Tipin Complex Coordinates an Intra-S Checkpoint Response to UV That Slows Replication Fork Displacement
Keziban Ünsal-Kaçmaz (2007)
Mechanisms of common fragile site instability.
T. Glover (2005)
Tipin/Tim1/And1 protein complex promotes Polα chromatin binding and sister chromatid cohesion
A. Errico (2009)
SUMO Modification Regulates BLM and RAD51 Interaction at Damaged Replication Forks
Karen J. Ouyang (2009)
Endogenous DNA replication stress results in expansion of dNTP pools and a mutator phenotype
Marta B Davidson (2012)
Replication checkpoint kinase Cds1 regulates Mus81 to preserve genome integrity during replication stress.
M. Kai (2005)
Replication protein A-mediated recruitment and activation of Rad17 complexes
L. Zou (2003)
PARP is activated at stalled forks to mediate Mre11‐dependent replication restart and recombination
H. Bryant (2009)
Thelander L. The Schizosaccharomyces pombe replication inhibitor Spd1 regulates ribonucleo‐ tide reductase activity and dNTPs by binding to the large Cdc22 subunit
P. Hakansson (2006)
A mutation in EXO1 defines separable roles in DNA mismatch repair and post-replication repair.
P. Tran (2007)
Effects of cytosine arabinoside and hydroxyurea on the synthesis of deoxyribonucleotides and DNA replication in L1210 cells.
M. Matsumoto (1990)
Repli‐ some stability at defective DNA replication forks is independent of S phase check‐ point kinases
G. De Piccoli (2012)
Arrested replication fork processing: interplay between checkpoints and recombination.
S. Lambert (2007)
Deoxycytidine kinase-deficient mutants of Chinese hamster ovary cells are hypersensitive to DNA alkylating agents.
M. Meuth (1983)
Human Tim/Timeless-interacting Protein, Tipin, Is Required for Efficient Progression of S Phase and DNA Replication Checkpoint*
N. Yoshizawa-Sugata (2007)
The ribonucleotide reductase inhibitor Sml1 is a new target of the Mec1/Rad53 kinase cascade during growth and in response to DNA damage
X. Zhao (2001)
Delineation of WRN helicase function with EXO1 in the replicational stress response.
M. Aggarwal (2010)
Mrc1, Tof1 and Csm3 inhibit CAG.CTG repeat instability by at least two mechanisms.
David F. Razidlo (2008)
The fission yeast Rad 32 ( Mre 11 )Rad 50Nbs 1 complex acts both upstream and downstream of checkpoint signaling in the S - phase DNA damage checkpoint
N. Willis (2010)
Ixr1 Is Required for the Expression of the Ribonucleotide Reductase Rnr1 and Maintenance of dNTP Pools
Olga Tsaponina (2011)
Cleavage of stalled forks by fission yeast Mus81/Eme1 in absence of DNA replication checkpoint.
Benoît Froget (2008)
Constitutively high dNTP concentration inhibits cell cycle progression and the DNA damage checkpoint in yeast Saccharomyces cerevisiae
A. Chabes (2007)
Failed gene conversion leads to extensive end processing and chromosomal rearrangements in fission yeast
Helen Tinline-Purvis (2009)
The Mechanisms of DNA Replication 206
The DNA poly‐ merase alpha-primase complex: multiple functions and interactions
M. Muzi-Falconi (2003)
Anaphase Onset Before Complete DNA Replication with Intact Checkpoint Responses
Jordi Torres-Rosell (2007)
Checkpoint-mediated control of replisome–fork association and signalling in response to replication pausing
C. Lucca (2004)
Mammalian single-strand break repair: mechanisms and links with chromatin.
K. Caldecott (2007)
A Mec1- and Rad53-dependent checkpoint controls late-firing origins of DNA replication
C. Santocanale (1998)
Highly mutagenic and severely imbalanced dNTP pools can escape detection by the S-phase checkpoint
D. Kumar (2010)
Developmental regulation of replication fork pausing in Xenopus laevis ribosomal RNA genes.
C. Maric (1999)
Human RPA phosphorylation by ATR stimulates DNA synthesis and prevents ssDNA accumulation during DNA-replication stress
V. M. Vassin (2009)
Cds1 Phosphorylation by Rad3-Rad26 Kinase Is Mediated by Forkhead-associated Domain Interaction with Mrc1*
K. Tanaka (2004)
Mrc1 and Tof1 promote replication fork progression and recovery independently of Rad53.
H. Tourrière (2005)
Two-stage mechanism for activation of the DNA replication checkpoint kinase Cds1 in fission yeast.
Yong-jie Xu (2006)
The structure-specific endonuclease Mus81 contributes to replication restart by generating double-strand DNA breaks
K. Hanada (2007)
Temporal separation of replication and recombination requires the intra-S checkpoint
P. Meister (2005)
Survival of DNA Damage in Yeast Directly Depends on Increased dNTP Levels Allowed by Relaxed Feedback Inhibition of Ribonucleotide Reductase
A. Chabes (2003)
A DNA replication-arrest site RTS1 regulates imprinting by determining the direction of replication at mat1 in S. pombe.
J. Dalgaard (2001)
The Fanconi anemia pathway is required for the DNA replication stress response and for the regulation of common fragile site stability.
N. Howlett (2005)
DNA Distress: Just Ring 9-1-1
M. Kemp (2009)
Sap1 Promotes the Association of the Replication Fork Protection Complex With Chromatin and Is Involved in the Replication Checkpoint in Schizosaccharomyces pombe
C. Noguchi (2007)
Swi1 Prevents Replication Fork Collapse and Controls Checkpoint Kinase Cds1
E. Noguchi (2003)
TopBP1 and DNA polymerase-α directly recruit the 9-1-1 complex to stalled DNA replication forks
S. Yan (2009)
DNA replication fork proteins.
U. Hübscher (2009)
Molecular cloning and analysis of Schizosaccharomyces pombe Reb1p: sequence-specific recognition of two sites in the far upstream rDNA intergenic spacer.
A. Zhao (1997)
The many facets of the Tim-Tipin protein families’ roles in chromosome biology
R. J. McFarlane (2010)
Induction of large DNA deletions by persistent nicks: a new hypothesis.
F. Hutchinson (1993)
Coupling of a rep‐ licative polymerase and helicase: a tau-DnaB interaction mediates rapid replication fork
S. Kim (1996)
Regulation of replication timing in fission yeast
S. M. Kim (2001)
Mechanisms of polar arrest of a replication fork
D. Kaplan (2009)
The yeast rad18 mutator specifically increases G.C----T.A transversions without reducing correction of G-A or C-T mismatches to G.C pairs.
Bernard A. Kunz (1991)
Mrc1 is required for normal progression of replication forks throughout chromatin in S. cerevisiae.
Shawn J Szyjka (2005)
DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis
J. Bártková (2005)
Mcl1p Is a Polymerase α Replication Accessory Factor Important for S-Phase DNA Damage Survival
D. R. Williams (2005)
Biochemical Interactions between Proteins and mat1 cis-Acting Sequences Required for Imprinting in Fission Yeast
B. Lee (2004)
Ribonucleotide reductase R2 gene expression and changes in drug sensitivity and genome stability.
A. Huang (1997)
Molecular coevolution of mammalian ribosomal gene terminator sequences and the transcription termination factor TTF-I.
R. Evers (1995)
Hydroxyurea Arrests DNA Replication by a Mechanism That Preserves Basal dNTP Pools*
Ahmet Koç (2004)
Complex mechanism of site‐specific DNA replication termination in fission yeast
Sandra Codlin (2003)
Mrc1 and DNA polymerase epsilon function together in linking DNA replication and the S phase checkpoint.
H. Lou (2008)
DNA damage and replication stress induced transcription of RNR genes is dependent on the Ccr4–Not complex
K. Mulder (2005)
Fork Reversal and ssDNA Accumulation at Stalled Replication Forks Owing to Checkpoint Defects
J. Sogo (2002)
Rad22Rad52-dependent repair of ribosomal DNA repeats cleaved by Slx1-Slx4 endonuclease.
S. Coulon (2006)
Maintenance of fork integrity at damaged DNA and natural pause sites.
H. Tourrière (2007)
Instability of a yeast centromere plasmid under conditions of thymine nucleotide stress.
S. E. Kohalmi (1988)
Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints
J. Bártková (2006)
The Fission Yeast Rad32(Mre11)–Rad50–Nbs1 Complex Acts Both Upstream and Downstream of Checkpoint Signaling in the S-Phase DNA Damage Checkpoint
Nicholas A. Willis (2010)
The fission yeast Rad 32 ( Mre 11 ) - Rad 50 - Nbs 1 complex acts both upstream and downstream of checkpoint signaling in the S - phase DNA damage checkpoint
N. Willis (2010)
Distinct RAD51 associations with RAD52 and BCCIP in response to DNA damage and replication stress.
Justin W Wray (2008)
Elevated dNTP levels suppress hyper-recombination in Saccharomyces cerevisiae S-phase checkpoint mutants
M. Fasullo (2010)
TTF‐I determines the chromatin architecture of the active rDNA promoter
G. Längst (1998)
Autoinhibition and Autoactivation of the DNA Replication Checkpoint Kinase Cds1
Yong-jie Xu (2009)
Roles of replication fork-interacting and Chk1-activating domains from Claspin in a DNA replication checkpoint response.
J. Lee (2005)
swi1- and swi3-dependent and independent replication fork arrest at the ribosomal DNA of Schizosaccharomyces pombe.
G. Krings (2004)
The DNA Polymerase ʱ-Primase Complex: Multiple Functions and Interactions
M. Muzi-Falconi (2003)
Regulation of Replication Termination by Reb1 Protein-Mediated Action at a Distance
S. K. Singh (2010)
Replication Fork Stalling at Natural Impediments
Ekaterina V. Mirkin (2007)
TopBP1 and DNA polymerase alpha-mediated recruitment of the 9-1-1 complex to stalled replication forks: Implications for a replication restart-based mechanism for ATR checkpoint activation
S. Yan (2009)
A single unbranched S-phase DNA damage and replication fork blockage checkpoint pathway
M. Marchetti (2002)
Mrc1 Marks Early-Firing Origins and Coordinates Timing and Efficiency of Initiation in Fission Yeast †
M. Hayano (2011)
dNTP pools determine fork progression and origin usage under replication stress
Jérôme Poli (2012)
Replication fork blockage by RTS1 at an ectopic site promotes recombination in fission yeast
Jong Sook Ahn (2005)
Checking on the fork: the DNA-replication stress-response pathway.
Alexander J. Osborn (2002)
Swi1 and Swi3 Are Components of a Replication Fork Protection Complex in Fission Yeast
E. Noguchi (2004)
GINS maintains association of Cdc45 with MCM in replisome progression complexes at eukaryotic DNA replication forks
Agnieszka Gambus (2006)
Role of deoxynucleoside triphosphate pools in the cytotoxic and mutagenic effects of DNA alkylating agents
M. Meuth (1981)
The Rad53 signal transduction pathway: Replication fork stabilization, DNA repair, and adaptation.
D. Branzei (2006)
Replisome stability at defective DNA replication forks is independent of S phase checkpoint kinases.
Giacomo De Piccoli (2012)
DNA synthesis provides the driving force to accelerate DNA unwinding by a helicase
Natalie M. Stano (2005)
Uncoupling of unwinding from DNA synthesis implies regulation of MCM helicase by Tof1/Mrc1/Csm3 checkpoint complex.
Marina N Nedelcheva (2005)
Cell-type-specific replication initiation programs set fragility of the FRA3B fragile site
A. Letessier (2011)
Replication in Hydroxyurea: It's a Matter of Time
G. Alvino (2007)
Mechanistic Insights into Replication Termination as Revealed by Investigations of the Reb1-Ter3 Complex of Schizosaccharomyces pombe
S. Biswas (2008)
Cell - typespecific replication initiation programs set fragility of the FRA 3 B fragile site
A. Letessier (2011)
Different requirements for the associa‐ tion of ATR-ATRIP and 9-1-1 to the stalled replication
Y. Kanoh (2006)
Mrc1 channels the DNA replication arrest signal to checkpoint kinase Cds1
K. Tanaka (2001)
Replication fork barriers: pausing for a break or stalling for time?
K. Labib (2007)
NBS1 cooperates with homologous recombination to counteract chromosome breakage during replication.
L. Brugmans (2009)
Induction of polyploidy by concentrated thymidine.
C. Potter (1971)
RAD51 and MRE11 dependent reassembly of uncoupled CMG helicase complex at collapsed replication forks
Yoshitami Hashimoto (2012)
Replication fork arrest, recombination and the maintenance of ribosomal DNA stability.
E. Tsang (2008)
Genome‐wide characterization of fission yeast DNA replication origins
Christian Heichinger (2006)
Replisome progression complex links DNA replication to sister chromatid cohesion in Xenopus egg extracts
H. Tanaka (2009)
Fission Yeast Swi1-Swi3 Complex Facilitates DNA Binding of Mrc1*
T. Tanaka (2010)
Replication stress induces genome-wide copy number changes in human cells that resemble polymorphic and pathogenic variants.
M. Arlt (2009)
MRC1-dependent scaling of the budding yeast DNA replication timing program.
A. Koren (2010)
Continued DNA Synthesis in Replication Checkpoint Mutants Leads to Fork Collapse
S. Sabatinos (2012)
Mcl1p is a polymerase alpha replication accessory factor important for S-phase DNA damage survival.
D. R. Williams (2005)
swi1 and swi3 Perform Imprinting, Pausing, and Termination of DNA Replication in S. pombe
J. Dalgaard (2000)
Unwinding the functions of the Pif1 family helicases.
Matthew L. Bochman (2010)
Different requirements for the association of ATR-ATRIP and 9-1-1 to the stalled replication forks.
Y. Kanoh (2006)
Replication Stress-Induced Chromosome Breakage Is Correlated with Replication Fork Progression and Is Preceded by Single-Stranded DNA Formation
W. Feng (2011)
Human Timeless and Tipin stabilize replication forks and facilitate sister-chromatid cohesion
A. R. Leman (2010)
Esc4/Rtt107 and the control of recombination during replication.
J. Chin (2006)
Replication fork pausing and recombination or "gimme a break".
R. Rothstein (2000)
Replication foci dynamics: replication patterns are modulated by S‐phase checkpoint kinases in fission yeast
P. Meister (2007)
Sgs1 function in the repair of DNA replication intermediates is separable from its role in homologous recombinational repair
K. Bernstein (2009)
A key role for Ctf4 in coupling the MCM2‐7 helicase to DNA polymerase α within the eukaryotic replisome
Agnieszka Gambus (2009)
Mrc1 transduces signals of DNA replication stress to activate Rad53
A. Alcasabas (2001)
Replication Checkpoint Protein Mrc1 Is Regulated by Rad3 and Tel1 in Fission Yeast
H. Zhao (2003)
RTS1-an eukaryotic terminator of replication.
S. Vengrova (2002)
The ATR barrier to replication-born DNA damage.
A. López-Contreras (2010)
Claspin, a novel protein required for the activation of Chk1 during a DNA replication checkpoint response in Xenopus egg extracts.
A. Kumagai (2000)
The DNA replication checkpoint response stabilizes stalled replication forks
M. Lopes (2001)
S-phase-specific activation of Cds1 kinase defines a subpathway of the checkpoint response in Schizosaccharomyces pombe.
H. Lindsay (1998)
Differential regulation of homologous recombination at DNA breaks and replication forks by the Mrc1 branch of the S‐phase checkpoint
C. Alabert (2009)
Homologous recombination restarts blocked replication forks at the expense of genome rearrangements by template exchange.
S. Lambert (2010)
Mrc1 phosphorylation in response to DNA replication stress is required for Mec1 accumulation at the stalled fork
M. Naylor (2009)
Ti‐ pin/Tim1/And1 protein complex promotes Pol alpha chromatin binding and sister chromatid cohesion
A. Errico (2009)
Dynamic regulatory interactions of rad51, rad52, and replication protein-a in recombination intermediates.
T. Sugiyama (2009)
Chromosome fragile sites.
F. E. Yoder (1985)
The Schizosaccharomyces pombe Replication Inhibitor Spd1 Regulates Ribonucleotide Reductase Activity and dNTPs by Binding to the Large Cdc22 Subunit*
P. Håkansson (2006)
The biochemical basis of 5-bromouracil- and 2-aminopurine-induced mutagenesis.
M. Goodman (1985)
Genome‐wide localization of pre‐RC sites and identification of replication origins in fission yeast
M. Hayashi (2007)
S-phase checkpoint proteins Tof1 and Mrc1 form a stable replication-pausing complex
Y. Katou (2003)
Csm3, Tof1, and Mrc1 Form a Heterotrimeric Mediator Complex That Associates with DNA Replication Forks
M. Bando (2009)
Interplay of replication checkpoints and repair proteins at stalled replication forks.
D. Branzei (2007)
Genomic mapping of single-stranded DNA in hydroxyurea-challenged yeasts identifies origins of replication
W. Feng (2006)
Termination of Mammalian rDNA Replication: Polar Arrest of Replication Fork Movement by Transcription Termination Factor TTF-I
Josef-Karl Gerber (1997)
Preserving the Replication Fork in Response to Nucleotide Starvation: Evading the Replication Fork Collapse Point
Mechanisms of mutagenesis in vivo due to imbalanced dNTP pools
D. Kumar (2011)
Rtf1-Mediated Eukaryotic Site-Specific Replication Termination
T. Eydmann (2008)
Evidence that POB1, a Saccharomyces cerevisiae protein that binds to DNA polymerase alpha, acts in DNA metabolism in vivo.
J. Miles (1992)
Reconstitution of DNA Strand Exchange Mediated by Rhp51 Recombinase and Two Mediators
Yumiko Kurokawa (2008)
Dynamic DNA helicase-DNA polymerase interactions assure processive replication fork movement.
S. Hamdan (2007)
Mammalian TIMELESS and Tipin are evolutionarily conserved replication fork-associated factors.
A. L. Gotter (2007)
Common fragile sites as targets for chromosome rearrangements.
M. Arlt (2006)
Coupling of a Replicative Polymerase and Helicase: A τ–DnaB Interaction Mediates Rapid Replication Fork Movement
S. Kim (1996)
Role of Saccharomyces Single-Stranded DNA-Binding Protein RPA in the Strand Invasion Step of Double-Strand Break Repair
X. Wang (2004)
Gimme a Break!
B. Friedlander (2009)
Replication Protein A and the Mre11·Rad50·Nbs1 Complex Co-localize and Interact at Sites of Stalled Replication Forks*
J. Robison (2004)
Double-Strand Break Repair-Independent Role for BRCA2 in Blocking Stalled Replication Fork Degradation by MRE11
K. Schlacher (2011)
Whither the replisome: Emerging perspectives on the dynamic nature of the DNA replication machinery
L. Langston (2009)
Schizosaccharomyces pombe Cds1Chk2 regulates homologous recombination at stalled replication forks through the phosphorylation of recombination protein Rad60
Izumi Miyabe (2009)
Minichromosome Maintenance Proteins Interact with Checkpoint and Recombination Proteins To Promote S-Phase Genome Stability
J. Bailis (2008)
Nucleoside analogues create DNA damage and sensitivity in fission yeast
S. A. Sabatinos (2012)
Sap1p Binds to Ter1 at the Ribosomal DNA of Schizosaccharomyces pombe and Causes Polar Replication Fork Arrest*
G. Krings (2005)
Monitoring S phase progression globally and locally using BrdU incorporation in TK(+) yeast strains.
A. Lengronne (2001)
Mechanism of action of hydroxyurea.
J. Yarbro (1992)
Cell-type-specific replication initiation programs set fragility of the FRA3B fragile
A. Letessier (2011)
Thelander L, and Rothstein R. The ribonucleotide reductase inhibitor Sml1 is a new target of the Mec1/Rad53 kinase cascade during growth and in response to DNA damage
X Zhao (2001)
Genome-Organizing Factors Top2 and Hmo1 Prevent Chromosome Fragility at Sites of S phase Transcription
Rodrigo Bermejo (2009)
Role of Blm and collaborating factors in recombination and survival following replication stress in Ustilago maydis.
Ninghui Mao (2009)
Changes of deoxyribonucleoside triphosphate pools induced by hydroxyurea and their relation to DNA synthesis.
V. Bianchi (1986)
Mrc1 is a replication fork component whose phosphorylation in response to DNA replication stress activates Rad53.
Alexander J. Osborn (2003)
Single-strand interruptions in replicating chromosomes cause double-strand breaks
A. Kuzminov (2001)
Claspin and the Activated Form of ATR-ATRIP Collaborate in the Activation of Chk1*
A. Kumagai (2004)
Tipin is required for stalled replication forks to resume DNA replication after removal of aphidicolin in Xenopus egg extracts
A. Errico (2007)
mcl1+, the Schizosaccharomyces pombe Homologue of CTF4, Is Important for Chromosome Replication, Cohesion, and Segregation
D. R. Williams (2002)
Centromere Replication Timing Determines Different Forms of Genomic Instability in Saccharomyces cerevisiae Checkpoint Mutants During Replication Stress
W. Feng (2009)
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