ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage.

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Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER 3rd, Hurov KE, Luo J, Bakalarski CE, Zhao Z, Solimini N, Lerenthal Y, Shiloh Y, Gygi SP, Elledge SJ

ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage.

Science. 2007 May 25;316(5828):1160-6.

PubMed ID
17525332 [ View in PubMed
]
Abstract

Cellular responses to DNA damage are mediated by a number of protein kinases, including ATM (ataxia telangiectasia mutated) and ATR (ATM and Rad3-related). The outlines of the signal transduction portion of this pathway are known, but little is known about the physiological scope of the DNA damage response (DDR). We performed a large-scale proteomic analysis of proteins phosphorylated in response to DNA damage on consensus sites recognized by ATM and ATR and identified more than 900 regulated phosphorylation sites encompassing over 700 proteins. Functional analysis of a subset of this data set indicated that this list is highly enriched for proteins involved in the DDR. This set of proteins is highly interconnected, and we identified a large number of protein modules and networks not previously linked to the DDR. This database paints a much broader landscape for the DDR than was previously appreciated and opens new avenues of investigation into the responses to DNA damage in mammals.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
RAF proto-oncogene serine/threonine-protein kinaseP04049Details
Serine--tRNA ligase, cytoplasmicP49591Details
Abelson tyrosine-protein kinase 2P42684Details
Beta-2 adrenergic receptorP07550Details
Sodium/hydrogen exchanger 1P19634Details
Cyclic AMP-responsive element-binding protein 1P16220Details
Mitogen-activated protein kinase 14Q16539Details
Deoxyhypusine synthaseP49366Details
Microtubule-associated protein 1AP78559Details
Poly [ADP-ribose] polymerase 1P09874Details
Kinesin-like protein KIF11P52732Details
Heat shock protein HSP 90-betaP08238Details
Peptidyl-prolyl cis-trans isomerase GQ13427Details
DNA-dependent protein kinase catalytic subunitP78527Details
DNA topoisomerase 2-betaQ02880Details
Probable ATP-dependent RNA helicase DDX6P26196Details
C-terminal-binding protein 1Q13363Details
Deoxycytidine kinaseP27707Details
Cellular tumor antigen p53P04637Details
Serine/threonine-protein kinase Chk1O14757Details
B-lymphocyte antigen CD19P15391Details
DNA polymerase epsilon catalytic subunit AQ07864Details
DNA polymerase epsilon subunit 4Q9NR33Details
Nuclear receptor coactivator 1Q15788Details
Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1Q13526Details
Heat shock cognate 71 kDa proteinP11142Details
CREB-binding proteinQ92793Details
Mediator of RNA polymerase II transcription subunit 1Q15648Details
Transitional endoplasmic reticulum ATPaseP55072Details
Kinesin-like protein KIF2CQ99661Details
Serine-protein kinase ATMQ13315Details
Heterogeneous nuclear ribonucleoprotein FP52597Details
Heat shock 70 kDa protein 4P34932Details
Far upstream element-binding protein 2Q92945Details
Heterochromatin protein 1-binding protein 3Q5SSJ5Details
Serine/threonine-protein kinase LATS1O95835Details
Serine/threonine-protein kinase OSR1O95747Details
V-type proton ATPase 116 kDa subunit a isoform 2Q9Y487Details
Eukaryotic translation initiation factor 4E-binding protein 1Q13541Details