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    Ubiquitin-like proteins in the DNA damage response: the next generation

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    Authors
    Da Costa, Isabelle C
    Schmidt, Christine K
    Affiliation
    Manchester Cancer Research Centre, Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, 555 Wilmslow Road, Manchester
    Issue Date
    2020
    
    Metadata
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    Abstract
    DNA 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.
    Citation
    Da 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
    Journal
    Essays in Biochemistry
    URI
    http://hdl.handle.net/10541/623854
    DOI
    10.1042/ebc20190095
    PubMed ID
    32451552
    Additional Links
    https://dx.doi.org/10.1042/ebc20190095
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1042/ebc20190095
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

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