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LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00003090naa a2200385 4500
001oai:DiVA.org:umu-79776
003SwePub
008130902s2013 | |||||||||||000 ||eng|
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-797762 URI
0247 a https://doi.org/10.1128/MCB.00474-132 DOI
040 a (SwePub)umu
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Hoch, Nicolas C4 aut
2451 0a Molecular basis of the essential s phase function of the rad53 checkpoint kinase
264 1c 2013
338 a print2 rdacarrier
520 a The essential yeast kinases Mec1 and Rad53, or human ATR and Chk1, are crucial for checkpoint responses to exogenous genotoxic agents, but why they are also required for DNA replication in unperturbed cells remains poorly understood. Here we report that even in the absence of DNA-damaging agents, the rad53-4AQ mutant, lacking the N-terminal Mec1 phosphorylation site cluster, is synthetic lethal with a deletion of the RAD9 DNA damage checkpoint adaptor. This phenotype is caused by an inability of rad53-4AQ to activate the downstream kinase Dun1, which then leads to reduced basal deoxynucleoside triphosphate (dNTP) levels, spontaneous replication fork stalling, and constitutive activation of and dependence on S phase DNA damage checkpoints. Surprisingly, the kinase-deficient rad53-K227A mutant does not share these phenotypes but is rendered inviable by additional phosphosite mutations that prevent its binding to Dun1. The results demonstrate that ultralow Rad53 catalytic activity is sufficient for normal replication of undamaged chromosomes as long as it is targeted toward activation of the effector kinase Dun1. Our findings indicate that the essential S phase function of Rad53 is comprised by the combination of its role in regulating basal dNTP levels and its compensatory kinase function if dNTP levels are perturbed.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinsk bioteknologix Medicinsk bioteknologi0 (SwePub)304012 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Medical Biotechnologyx Medical Biotechnology0 (SwePub)304012 hsv//eng
7001 a Chen, Eric S-W4 aut
7001 a Buckland, Robert,d 1976-u Umeå universitet,Institutionen för medicinsk kemi och biofysik4 aut0 (Swepub:umu)robu0005
7001 a Wang, Shun-Chung4 aut
7001 a Fazio, Alessandro4 aut
7001 a Hammet, Andrew4 aut
7001 a Pellicioli, Achille4 aut
7001 a Chabes, Andreiu Umeå universitet,Institutionen för medicinsk kemi och biofysik,Molekylär Infektionsmedicin, Sverige (MIMS)4 aut0 (Swepub:umu)anch0002
7001 a Tsai, Ming-Daw4 aut
7001 a Heierhorst, Jörg4 aut
7102 a Umeå universitetb Institutionen för medicinsk kemi och biofysik4 org
7730 t Molecular and Cellular Biologyg 33:16, s. 3202-3213q 33:16<3202-3213x 0270-7306x 1098-5549
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-79776
8564 8u https://doi.org/10.1128/MCB.00474-13

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