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DNA damage checkpoint kinases in cancer

Lookup NU author(s): Hannah Smith, Harriet Southgate, Professor Deborah Tweddle, Professor Nicola CurtinORCiD

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Abstract

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.

Publication metadata

Author(s): Smith HL, Southgate H, Tweddle DA, Curtin NJ

Publication type: Article

Publication status: Published

Journal: Expert Reviews in Molecular Medicine

Year: 2020

Volume: 22

Online publication date: 08/06/2020

Acceptance date: 02/04/2018

ISSN (electronic): 1462-3994

Publisher: Cambridge University Press

URL: https://doi.org/10.1017/erm.2020.3

DOI: 10.1017/erm.2020.3

PubMed id: 32508294

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