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ATR as a therapeutic target

Lookup NU author(s): Fiona Middleton, Professor Nicola Curtin

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Abstract

© Springer Science+Business Media, LLC 2013. All rights are reserved. Ataxia Telangiectasia Mutated and Rad3-related (ATR) is a vital sensor of a variety of DNA lesions and is critical to cell cycle arrest at the S and G2 checkpoints as well as initiation of DNA repair via homologous recombination repair (HRR). ATR is a member of the PI-3K like family of kinases (PIKKs), which include Ataxia Telangiectasia Mutated (ATM) and DNA-PKCS(DNA-dependent protein kinase catalytic subunit) [1]; protein kinases that are also involved in the complex network of DNA damage signalling and repair mechanisms known as the DNA damage response (DDR). The DDR comprises sensor proteins which detect the DNA damage and signal to transducer proteins, e.g. p53 and checkpoint kinases which then transmit this information to downstream effector proteins. These effectors activate the appropriate damage response, be it cell cycle arrest and DNA repair or apoptosis. Many of the phosphorylation substrates of ATR are also common to ATM, and the two are both involved in HRR in response to double strand breaks (DSBs). There is also crosstalk between the two PIKKs. ATM and ATR phosphorylate >900 sites on >700 proteins in response to DNA damage induced, experimentally, highlighting the complexity of the network. The majority of phosphorylated proteins are involved in DNA replication, recombination and repair plus cell cycle regulation [2].


Publication metadata

Author(s): Middleton FK, Curtin NJ

Publication type: Book Chapter

Publication status: Published

Book Title: Advances in DNA Repair in Cancer Therapy

Year: 2013

Pages: 211-228

Online publication date: 03/11/2012

Publisher: Springer

Place Published: New York

URL: https://doi.org/10.1007/978-1-4614-4741-2_10

DOI: 10.1007/978-1-4614-4741-2_10

Library holdings: Search Newcastle University Library for this item

ISBN: 9781461447412


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