Ubiquitin-like proteins in the DNA damage response: the next generation
AffiliationManchester Cancer Research Centre, Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, 555 Wilmslow Road, Manchester
MetadataShow full item record
AbstractDNA suffers constant insult from a variety of endogenous and exogenous sources. To deal with the arising lesions, cells have evolved complex and coordinated pathways, collectively termed the DNA damage response (DDR). Importantly, an improper DDR can lead to genome instability, premature ageing and human diseases, including cancer as well as neurodegenerative disorders. As a crucial process for cell survival, regulation of the DDR is multi-layered and includes several post-translational modifications. Since the discovery of ubiquitin in 1975 and the ubiquitylation cascade in the early 1980s, a number of ubiquitin-like proteins (UBLs) have been identified as post-translational modifiers. However, while the importance of ubiquitin and the UBLs SUMO and NEDD8 in DNA damage repair and signalling is well established, the roles of the remaining UBLs in the DDR are only starting to be uncovered. Herein, we revise the current status of the UBLs ISG15, UBL5, FAT10 and UFM1 as emerging co-regulators of DDR processes. In fact, it is becoming clear that these post-translational modifiers play important pleiotropic roles in DNA damage and/or associated stress-related cellular responses. Expanding our understanding of the molecular mechanisms underlying these emerging UBL functions will be fundamental for enhancing our knowledge of the DDR and potentially provide new therapeutic strategies for various human diseases including cancer.
CitationDa Costa IC, Schmidt CK. Ubiquitin-like proteins in the DNA damage response: the next generation. Wu Q, editor. Essays in Biochemistry [Internet]. 2020 May 26;64(5):737–52
JournalEssays in Biochemistry
- Ubiquitin-like modifications in the DNA damage response.
- Authors: Wang Z, Zhu WG, Xu X
- Issue date: 2017 Oct
- Ubiquitylation, neddylation and the DNA damage response.
- Authors: Brown JS, Jackson SP
- Issue date: 2015 Apr
- More than Meets the ISG15: Emerging Roles in the DNA Damage Response and Beyond.
- Authors: Sandy Z, da Costa IC, Schmidt CK
- Issue date: 2020 Nov 15
- Ubiquitin-Like Modifiers: Emerging Regulators of Protozoan Parasites.
- Authors: Karpiyevich M, Artavanis-Tsakonas K
- Issue date: 2020 Oct 3
- Modification by ubiquitin-like proteins: significance in apoptosis and autophagy pathways.
- Authors: Cajee UF, Hull R, Ntwasa M
- Issue date: 2012