Abstract
The maintenance of genome stability requires dedicated DNA repair processes and pathways that are essential for the faithful duplication and propagation of chromosomes. These DNA repair mechanisms counteract the potentially deleterious impact of the frequent genotoxic challenges faced by cells from both exogenous and endogenous agents. Intrinsic to these mechanisms, cells have an arsenal of protein factors that can be utilised to promote repair processes in response to DNA lesions. Orchestration of the protein factors within the various cellular DNA repair pathways is performed, in part, by post-translational modifications, such as phosphorylation, ubiquitin, SUMO and other ubiquitin-like modifiers (UBLs). In this review, we firstly explore recent advances in the tools for identifying factors involved in both DNA repair and ubiquitin signaling pathways. We then expand on this by evaluating the growing repertoire of proteomic, biochemical and structural techniques available to further understand the mechanistic basis by which these complex modifications regulate DNA repair. Together, we provide a snapshot of the range of methods now available to investigate and decode how ubiquitin signaling can promote DNA repair and maintain genome stability in mammalian cells.
Highlights
Maintenance of genome stability is critically important for cellular fitness and organismal survival
We highlight the methodologies used to make these discoveries, potential limitations, and how these tools can be evolved and used to answer remaining questions. To do this we focus on discoveries in the three broad areas of genetics, proteomics and biochemistry, which have helped illuminate our fundamental understanding of DNA damage response (DDR) mechanisms and the role that ubiquitin plays within them, as well as how this understanding can be harnessed for therapeutic purposes
The DDR is a highly inter-related signaling network, whereby DNA lesions may be channeled from a primary DNA repair pathway to another back-up DNA repair pathway, if the primary DNA repair pathway fails for some reason
Summary
Reviewed by: Christine Schmidt, The University of Manchester, United Kingdom Katharina F. The maintenance of genome stability requires dedicated DNA repair processes and pathways that are essential for the faithful duplication and propagation of chromosomes. These DNA repair mechanisms counteract the potentially deleterious impact of the frequent genotoxic challenges faced by cells from both exogenous and endogenous agents. Intrinsic to these mechanisms, cells have an arsenal of protein factors that can be utilised to promote repair processes in response to DNA lesions. We provide a snapshot of the range of methods available to investigate and decode how ubiquitin signaling can promote DNA repair and maintain genome stability in mammalian cells
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