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Phosphorylation-dependent assembly of DNA damage response systems and the central roles of TOPBP1
journal contribution
posted on 2023-06-10, 01:22 authored by Matthew Day, Antony OliverAntony Oliver, Laurence PearlLaurence PearlThe cellular response to DNA damage (DDR) that causes replication collapse and/or DNA double strand breaks, is characterised by a massive change in the post-translational modifications (PTM) of hundreds of proteins involved in the detection and repair of DNA damage, and the communication of the state of damage to the cellular systems that regulate replication and cell division. A substantial proportion of these PTMs involve targeted phosphorylation, which among other effects, promotes the formation of multiprotein complexes through the specific binding of phosphorylated motifs on one protein, by specialised domains on other proteins. Understanding the nature of these phosphorylation mediated interactions allows definition of the pathways and networks that coordinate the DDR, and helps identify new targets for therapeutic intervention that may be of benefit in the treatment of cancer, where DDR plays a key role. In this review we summarise the present understanding of how phosphorylated motifs are recognised by BRCT domains, which occur in many DDR proteins. We particularly focus on TOPBP1 – a multi-BRCT domain scaffold protein with essential roles in replication and the repair and signalling of DNA damage.
Funding
Structural Biology of DNA Damage Response and Repair Mechanisms; G2176; CANCER RESEARCH UK; C302/A24386
History
Publication status
- Published
File Version
- Published version
Journal
DNA RepairISSN
1568-7864Publisher
ElsevierExternal DOI
Volume
108Page range
1-11Article number
a103232Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2021-10-12First Open Access (FOA) Date
2021-10-12First Compliant Deposit (FCD) Date
2021-10-11Usage metrics
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