About this Research Topic
To overcome DNA injury, cells employ several strategies that act synergistically to increase chances of survival. Posttranslational modifications by ubiquitin or SUMO have been shown to be an effective mechanism to accomplish this. SUMOylation (as ubiquitination) is achieved by the sequential action of three enzymes (E1, E2, E3). Ultimately, the E3 ligases are responsible to potentiate a SUMO conjugation response. In vivo, most substrates require the presence of a SUMO E3 enzyme, which facilitates the transfer of SUMO to the acceptor lysine of a substrate by enhancing the interaction between the SUMO-charged Ubc9 and the substrate protein.
Through the use of modern mass spectrometry techniques, several groups of proteins have been identified as targets for SUMOylation in conditions of DNA damage, a phenomenon named protein group PTM modification. Although vertebrates possess only a few bona-fide SUMO E3-ligases, in recent years other proteins (such as TRIM proteins, SUV39h1 methyltransferase, SLX4 SUMOylate xeroderma pigmentosum group-F (XPF)) have also been reported as SUMO conjugation enhancers. Since there is a lot to discover about emerging E3 ligases, it is still of great interest to expand the knowledge about how these different ligases are recruited to the distinct types of DNA breaking points and narrow down the subset of proteins that are modified by each ligase individually in other to discriminate between the mechanisms by which they orchestrate DNA damage repair. Moreover, is also know that E3 ligases and DNA repair proteins are decorated with motifs that non-covalently bind SUMO, named SUMO interaction motifs (SIM). These small patches connect the protein carriers to the SUMOylated proteins or to the ligases themselves, acting like a glue, forming a network of interactive partners around DNA damage sites. Moreover, SIM present in E3 ligases can enhance conjugation by docking E2 in an optimal conformation for discharge. Since these motifs present sequence promiscuity making them difficult to be predicted by sequence analyses, most of them are yet to be discovered.
This Research Topic will therefore provide a platform to encourage and spotlight this emerging and important research trend, and will welcome submissions including, but not limited to, the following themes:
• Understanding the mechanism by which SUMO E3 ligases are recruited to the DNA damage sites. Particularly by the identification of DNA binding motifs, how they interact with the double-strand breaks DNA and the effects of natural mutations.
• Identification of the subset of proteins (targets) that are modified by any individual E3 ligase in DNA damage context.
• Identification of SUMO Interaction Motifs (SIM) in E3 ligases and DNA repair proteins.
• Understanding the role of SUMO Interaction Motifs (SIM) in the formation of interactive networks and how they impact in the efficiency of different E3 ligases.
Through the use of modern mass spectrometry techniques, several groups of proteins have been identified as targets for SUMOylation in conditions of DNA damage, a phenomenon named protein group PTM modification. Although vertebrates possess only a few bona-fide SUMO E3-ligases, in recent years other proteins (such as TRIM proteins, SUV39h1 methyltransferase, SLX4 SUMOylate xeroderma pigmentosum group-F (XPF)) have also been reported as SUMO conjugation enhancers. Since there is a lot to discover about emerging E3 ligases, it is still of great interest to expand the knowledge about how these different ligases are recruited to the distinct types of DNA breaking points and narrow down the subset of proteins that are modified by each ligase individually in other to discriminate between the mechanisms by which they orchestrate DNA damage repair. Moreover, is also know that E3 ligases and DNA repair proteins are decorated with motifs that non-covalently bind SUMO, named SUMO interaction motifs (SIM). These small patches connect the protein carriers to the SUMOylated proteins or to the ligases themselves, acting like a glue, forming a network of interactive partners around DNA damage sites. Moreover, SIM present in E3 ligases can enhance conjugation by docking E2 in an optimal conformation for discharge. Since these motifs present sequence promiscuity making them difficult to be predicted by sequence analyses, most of them are yet to be discovered.
This Research Topic will therefore provide a platform to encourage and spotlight this emerging and important research trend, and will welcome submissions including, but not limited to, the following themes:
• Understanding the mechanism by which SUMO E3 ligases are recruited to the DNA damage sites. Particularly by the identification of DNA binding motifs, how they interact with the double-strand breaks DNA and the effects of natural mutations.
• Identification of the subset of proteins (targets) that are modified by any individual E3 ligase in DNA damage context.
• Identification of SUMO Interaction Motifs (SIM) in E3 ligases and DNA repair proteins.
• Understanding the role of SUMO Interaction Motifs (SIM) in the formation of interactive networks and how they impact in the efficiency of different E3 ligases.
Keywords: DNA repair, SUMO, SIM, E3 ligase
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