http://purl.uniprot.org/citations/19805627 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/19805627 | http://www.w3.org/2000/01/rdf-schema#comment | "The Tim (Timeless)-Tipin complex has been proposed to maintain genome stability by facilitating ATR-mediated Chk1 activation. However, as a replisome component, Tim-Tipin has also been suggested to couple DNA unwinding to synthesis, an activity expected to suppress single-stranded DNA (ssDNA) accumulation and limit ATR-Chk1 pathway engagement. We now demonstrate that Tim-Tipin depletion is sufficient to increase ssDNA accumulation at replication forks and stimulate ATR activity during otherwise unperturbed DNA replication. Notably, suppression of the ATR-Chk1 pathway in Tim-Tipin-deficient cells completely abrogates nucleotide incorporation in S phase, indicating that the ATR-dependent response to Tim-Tipin depletion is indispensible for continued DNA synthesis. Replication failure in ATR/Tim-deficient cells is strongly associated with synergistic increases in H2AX phosphorylation and DNA double-strand breaks, suggesting that ATR pathway activation preserves fork stability in instances of Tim-Tipin dysfunction. Together, these experiments indicate that the Tim-Tipin complex stabilizes replication forks both by preventing the accumulation of ssDNA upstream of ATR-Chk1 function and by facilitating phosphorylation of Chk1 by ATR."xsd:string |
http://purl.uniprot.org/citations/19805627 | http://purl.org/dc/terms/identifier | "doi:10.1083/jcb.200905006"xsd:string |
http://purl.uniprot.org/citations/19805627 | http://purl.uniprot.org/core/author | "Brown E.J."xsd:string |
http://purl.uniprot.org/citations/19805627 | http://purl.uniprot.org/core/author | "Smith K.D."xsd:string |
http://purl.uniprot.org/citations/19805627 | http://purl.uniprot.org/core/author | "Fu M.A."xsd:string |
http://purl.uniprot.org/citations/19805627 | http://purl.uniprot.org/core/date | "2009"xsd:gYear |
http://purl.uniprot.org/citations/19805627 | http://purl.uniprot.org/core/name | "J Cell Biol"xsd:string |
http://purl.uniprot.org/citations/19805627 | http://purl.uniprot.org/core/pages | "15-23"xsd:string |
http://purl.uniprot.org/citations/19805627 | http://purl.uniprot.org/core/title | "Tim-Tipin dysfunction creates an indispensible reliance on the ATR-Chk1 pathway for continued DNA synthesis."xsd:string |
http://purl.uniprot.org/citations/19805627 | http://purl.uniprot.org/core/volume | "187"xsd:string |
http://purl.uniprot.org/citations/19805627 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/19805627 |
http://purl.uniprot.org/citations/19805627 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/19805627 |
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http://purl.uniprot.org/uniprot/#_A0A1L1STK1-mappedCitation-19805627 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19805627 |
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http://purl.uniprot.org/uniprot/#_Q3U574-mappedCitation-19805627 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19805627 |
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http://purl.uniprot.org/uniprot/#_Q3UXJ0-mappedCitation-19805627 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19805627 |