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Lookup NU author(s): Hannah Smith,
Professor Deborah Tweddle,
Professor Nicola CurtinORCiD
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DNA damage response (DDR) pathway prevents high level endogenous and environmental DNA damage being replicated and passed on to the next generation of cells via an orchestrated and integrated network of cell cycle checkpoint signalling and DNA repair pathways. Depending on the type of damage, and where in the cell cycle it occurs different pathways are involved, with the ATM-CHK2-p53 pathway controlling the G1 checkpoint or ATR-CHK1-Wee1 pathway controlling the S and G2/M checkpoints. Loss of G1 checkpoint control is common in cancer through TP53, ATM mutations, Rb loss or cyclin E overexpression, providing a stronger rationale for targeting the S/G2 checkpoints. This review will focus on the ATM-CHK2-p53-p21 pathway and the ATR-CHK1-WEE1 pathway and ongoing efforts to target these pathways for patient benefit.
Author(s): Smith HL, Southgate H, Tweddle DA, Curtin NJ
Publication type: Article
Publication status: Published
Journal: Expert Reviews in Molecular Medicine
Online publication date: 08/06/2020
Acceptance date: 02/04/2018
ISSN (electronic): 1462-3994
Publisher: Cambridge University Press
PubMed id: 32508294
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