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Genes Dev
2007 Apr 15;218:898-903. doi: 10.1101/gad.1522607.
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The structural determinants of checkpoint activation.
MacDougall CA
,
Byun TS
,
Van C
,
Yee MC
,
Cimprich KA
.
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Here, we demonstrate that primed, single-stranded DNA (ssDNA) is sufficient for activation of the ATR-dependent checkpoint pathway in Xenopus egg extracts. Using this structure, we define the contribution of the 5'- and 3'-primer ends to Chk1 activation when replication is blocked and ongoing. In addition, we show that although ssDNA is not sufficient for checkpoint activation, the amount of ssDNA adjacent to the primer influences the level of Chk1 phosphorylation. These observations define the minimal DNA requirements for checkpoint activation and suggest that primed ssDNA represents a common checkpoint activating-structure formed following many types of damage.
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17437996
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Ahn,
The Chk2 protein kinase.
2004,
Pubmed
Blow,
Preventing re-replication of chromosomal DNA.
2005,
Pubmed
Byun,
Functional uncoupling of MCM helicase and DNA polymerase activities activates the ATR-dependent checkpoint.
2005,
Pubmed
,
Xenbase
Cortez,
Unwind and slow down: checkpoint activation by helicase and polymerase uncoupling.
2005,
Pubmed
Ellison,
Biochemical characterization of DNA damage checkpoint complexes: clamp loader and clamp complexes with specificity for 5' recessed DNA.
2003,
Pubmed
Garcia,
Identification and functional analysis of TopBP1 and its homologs.
2005,
Pubmed
Hickson,
Identification and characterization of a novel and specific inhibitor of the ataxia-telangiectasia mutated kinase ATM.
2004,
Pubmed
Huang,
Human nucleotide excision nuclease removes thymine dimers from DNA by incising the 22nd phosphodiester bond 5' and the 6th phosphodiester bond 3' to the photodimer.
1992,
Pubmed
Kumagai,
TopBP1 activates the ATR-ATRIP complex.
2006,
Pubmed
,
Xenbase
Kumagai,
Claspin, a novel protein required for the activation of Chk1 during a DNA replication checkpoint response in Xenopus egg extracts.
2000,
Pubmed
,
Xenbase
Lee,
Roles of replication fork-interacting and Chk1-activating domains from Claspin in a DNA replication checkpoint response.
2005,
Pubmed
,
Xenbase
Liu,
Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint.
2000,
Pubmed
Lopes,
Multiple mechanisms control chromosome integrity after replication fork uncoupling and restart at irreparable UV lesions.
2006,
Pubmed
Lupardus,
Phosphorylation of Xenopus Rad1 and Hus1 defines a readout for ATR activation that is independent of Claspin and the Rad9 carboxy terminus.
2006,
Pubmed
,
Xenbase
Lupardus,
A requirement for replication in activation of the ATR-dependent DNA damage checkpoint.
2002,
Pubmed
,
Xenbase
Machida,
Right place, right time, and only once: replication initiation in metazoans.
2005,
Pubmed
Majka,
Replication protein A directs loading of the DNA damage checkpoint clamp to 5'-DNA junctions.
2006,
Pubmed
Majka,
The checkpoint clamp activates Mec1 kinase during initiation of the DNA damage checkpoint.
2006,
Pubmed
Marini,
DNA nucleotide excision repair-dependent signaling to checkpoint activation.
2006,
Pubmed
McGarry,
Geminin, an inhibitor of DNA replication, is degraded during mitosis.
1998,
Pubmed
,
Xenbase
Méchali,
DNA synthesis in a cell-free system from Xenopus eggs: priming and elongation on single-stranded DNA in vitro.
1982,
Pubmed
,
Xenbase
Melo,
A unified view of the DNA-damage checkpoint.
2002,
Pubmed
,
Xenbase
Michael,
Activation of the DNA replication checkpoint through RNA synthesis by primase.
2000,
Pubmed
,
Xenbase
Pacek,
A requirement for MCM7 and Cdc45 in chromosome unwinding during eukaryotic DNA replication.
2004,
Pubmed
,
Xenbase
Parrilla-Castellar,
Dial 9-1-1 for DNA damage: the Rad9-Hus1-Rad1 (9-1-1) clamp complex.
2004,
Pubmed
Shechter,
Regulation of DNA replication by ATR: signaling in response to DNA intermediates.
2004,
Pubmed
,
Xenbase
Shechter,
ATR and ATM regulate the timing of DNA replication origin firing.
2004,
Pubmed
,
Xenbase
Stadlbauer,
DNA replication in vitro by recombinant DNA-polymerase-alpha-primase.
1994,
Pubmed
Stokes,
DNA replication is required for the checkpoint response to damaged DNA in Xenopus egg extracts.
2002,
Pubmed
,
Xenbase
Tercero,
A central role for DNA replication forks in checkpoint activation and response.
2003,
Pubmed
Walter,
Regulated chromosomal DNA replication in the absence of a nucleus.
1998,
Pubmed
,
Xenbase
Walter,
Initiation of eukaryotic DNA replication: origin unwinding and sequential chromatin association of Cdc45, RPA, and DNA polymerase alpha.
2000,
Pubmed
,
Xenbase
Ward,
UV-induced ataxia-telangiectasia-mutated and Rad3-related (ATR) activation requires replication stress.
2004,
Pubmed
You,
The role of single-stranded DNA and polymerase alpha in establishing the ATR, Hus1 DNA replication checkpoint.
2002,
Pubmed
,
Xenbase
Zhou,
The DNA damage response: putting checkpoints in perspective.
2000,
Pubmed
Zou,
Single- and double-stranded DNA: building a trigger of ATR-mediated DNA damage response.
2007,
Pubmed
Zou,
Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes.
2003,
Pubmed
Zou,
Replication protein A-mediated recruitment and activation of Rad17 complexes.
2003,
Pubmed