Phosphorylation-dependent assembly of DNA damage response systems and the central roles of TOPBP1
By M. Day, A. Oliver, L. Pearl. 2021
34 citations recorded by the source corpus.
The 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.
Subfields: Cell Biology, Molecular Biology, Oncology
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Cell Biology
In Molecular Biology
In Oncology
Citations in the corpus
- In silico protein interaction screening uncovers DONSON’s role in replication initiation (2023, background): “3E), consistent with the fact that the essential TOPBP1 BRCT domain that contacts DONSON (BRCT3) is not predicted to bind phospho-peptides ( 37 ).”
- DNSN-1 recruits GINS for CMG helicase assembly during DNA replication initiation in C. elegans (2023, unknown): “Finally, the metazoan orthologue of yeast Dpb11, known variously as TOPBP1 or MUS101, contains more BRCT domains than Dpb11 (31), and a study of Xenopus TOPBP1 indicated that BRCTs 4-8 are dispensable for replication initiation (32), despite containing the presumed binding site for RECQL4.”