Non-catalytic function for ATR in the checkpoint response.

Non-catalytic function for ATR in the checkpoint response. Research Abstract Details 

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Non-catalytic function for ATR in the checkpoint response. Abstract Text:

Troy D McSherry,Ana A Kitazono,Ali Javaheri,Stephen J Kron,Paul R Mueller,

The ATR family of checkpoint kinases is essential for an appropriate response to genomic insults in eukaryotes. Included in this family are Mei-41 in Drosophila, Mec1 inS. cerevisiae, Rad3 in S. pombe, and ATR in vertebrates. These large kinases phosphorylateand modify multiple cell cycle and checkpoint factors, leading to cell cycle arrest, DNA repair, and induction of apoptosis. The catalytic domain of all ATR family members comprises only a fraction of the total protein. Here, we show that the non-catalytic portion of ATR has a conserved function in the checkpoint response. Expression of either wild type or various kinase defective forms of Xenopus ATR (XATR) in S. cerevisiae mec1 mutants suppresses the checkpoint defect and induces a DNA damage dependent mitotic cell cycle arrest. This suppression requires the presence of yeast Ddc2 and Rad9 but functions independently of Rad9 modification and Rad53 activation. Our results indicate that XATR is not functioning through the established mitotic checkpoint pathways. Instead, we find that the XATR suppression of the mec1 mutant checkpoint defect requires the spindle checkpoint factors Mad1 and Mad2, suggesting a role for XATR in the spindle assembly checkpoint. Finally, we show that a yeast strain expressing a truncated, kinase domain deleted form of mec1 from the endogenous locus is partially checkpoint proficient and induces a mitotic cell cycle arrest in a Mad2 dependent manner. Thus, the link between the non-catalytic region of the ATR kinase family and the spindle checkpoint pathway is conserved.

Non-catalytic function for ATR in the checkpoint response. Publishing Authors By Initials

TD McSherry,AA Kitazono,A Javaheri,SJ Kron,PR Mueller,

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Non-catalytic function for ATR in the checkpoint response. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Cell cycle (Georgetown, Tex.)

VOLUME: 6

Page Numbers: 2019-30

Journal Abbreviation: Cell Cycle

ISSN: 1551-4005

DAY: 6

MONTH: 06

YEAR: 2007

Non-catalytic function for ATR in the checkpoint response. Information

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LANGUAGE: eng

NlmUniqueID: 101137841

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Grant and Affiliation Information for Non-catalytic function for ATR in the checkpoint response.

AFFILIATION: Center for Molecular Oncology, University of Chicago, Chicago, Illinois, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: R01 GM60443

ACRONYM: GM

MEDLINETA: Cell Cycle

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