Dearlove, Emily L. and Chatrin, Chatrin and Buetow, Lori and Ahmed, Syed F. and Schmidt, Tobias and Bushell, Martin and Smith, Brian O. and Huang, Danny T. (2024) DTX3L ubiquitin ligase ubiquitinates single-stranded nucleic acids. eLife, 13: RP98070. ISSN 2050-084X
AI Summary:
The study reveals that DTX3L, a member of the DELTEX E3 ligase family, can directly ubiquitinate single-stranded DNA and RNA.AI Topics:
Ubiquitination typically involves covalent linking of ubiquitin (Ub) to a lysine residue on a protein substrate. Recently, new facets of this process have emerged, including Ub modification of non-proteinaceous substrates like ADP-ribose by the DELTEX E3 ligase family. Here, we show that the DELTEX family member DTX3L expands this non-proteinaceous substrate repertoire to include single-stranded DNA and RNA. Although the N-terminal region of DTX3L contains single-stranded nucleic acid binding domains and motifs, the minimal catalytically competent fragment comprises the C-terminal RING and DTC domains (RD). DTX3L-RD catalyses ubiquitination of the 3’-end of single-stranded DNA and RNA, as well as double-stranded DNA with a 3’ overhang of two or more nucleotides. This modification is reversibly cleaved by deubiquitinases. NMR and biochemical analyses reveal that the DTC domain binds single-stranded DNA and facilitates the catalysis of Ub transfer from RING-bound E2-conjugated Ub. Our study unveils the direct ubiquitination of nucleic acids by DTX3L, laying the groundwork for understanding its functional implications.
Dearlove, Emily L.
Author
Dearlove, Emily L. and Chatrin, Chatrin and Buetow, Lori and Ahmed, Syed F. and Schmidt, Tobias and Bushell, Martin and Smith, Brian O. and Huang, Danny T. (2024) DTX3L ubiquitin ligase ubiquitinates single-stranded nucleic acids. eLife, 13: RP98070. ISSN 2050-084X
See full publications listChatrin, Chatrin
Author
Dearlove, Emily L. and Chatrin, Chatrin and Buetow, Lori and Ahmed, Syed F. and Schmidt, Tobias and Bushell, Martin and Smith, Brian O. and Huang, Danny T. (2024) DTX3L ubiquitin ligase ubiquitinates single-stranded nucleic acids. eLife, 13: RP98070. ISSN 2050-084X
See full publications listBuetow, Lori
Author
Bohlen, Jonathan and Bagarić, Ivan and Vatovec, Taja and Ogishi, Masato and Ahmed, Syed F. and Cederholm, Axel and Buetow, Lori and Sobrino, Steicy and Le Floc’h, Corentin and Arango-Franco, Carlos A. and Seabra, Luis and Michelet, Marine and Barzaghi, Federica and Leardini, Davide and Saettini, Francesco and Vendemini, Francesca and Baccelli, Francesco and Catala, Albert and Gambineri, Eleonora and Veltroni, Marinella and Aguilar de la Red, Yurena and Rice, Gillian I. and Consonni, Filippo and Berteloot, Laureline and Largeaud, Laetitia and Conti, Francesca and Roullion, Cécile and Masson, Cécile and Bessot, Boris and Seeleuthner, Yoann and Le Voyer, Tom and Rinchai, Darawan and Rosain, Jérémie and Neehus, Anna-Lena and Erazo-Borrás, Lucia and Li, Hailun and Janda, Zarah and Cho, En-Jui and Muratore, Edoardo and Soudée, Camille and Lainé, Candice and Delabesse, Eric and Goulvestre, Claire and Ma, Cindy S. and Puel, Anne and Tangye, Stuart G. and André, Isabelle and Bole-Feysot, Christine and Abel, Laurent and Erlacher, Miriam and Zhang, Shen-Ying and Béziat, Vivien and Lagresle-Peyrou, Chantal and Six, Emmanuelle and Pasquet, Marlène and Alsina, Laia and Aiuti, Alessandro and Zhang, Peng and Crow, Yanick J. and Landegren, Nils and Masetti, Riccardo and Huang, Danny T. and Casanova, Jean-Laurent and Bustamante, Jacinta (2024) Autoinflammation in patients with leukocytic CBL loss of heterozygosity is caused by constitutive ERK-mediated monocyte activation. Journal of Clinical Investigation, 134 (20): e181604. ISSN 0021-9738
Dearlove, Emily L. and Chatrin, Chatrin and Buetow, Lori and Ahmed, Syed F. and Schmidt, Tobias and Bushell, Martin and Smith, Brian O. and Huang, Danny T. (2024) DTX3L ubiquitin ligase ubiquitinates single-stranded nucleic acids. eLife, 13: RP98070. ISSN 2050-084X
See full publications listAhmed, S. Faisal
Author
Bohlen, Jonathan and Bagarić, Ivan and Vatovec, Taja and Ogishi, Masato and Ahmed, Syed F. and Cederholm, Axel and Buetow, Lori and Sobrino, Steicy and Le Floc’h, Corentin and Arango-Franco, Carlos A. and Seabra, Luis and Michelet, Marine and Barzaghi, Federica and Leardini, Davide and Saettini, Francesco and Vendemini, Francesca and Baccelli, Francesco and Catala, Albert and Gambineri, Eleonora and Veltroni, Marinella and Aguilar de la Red, Yurena and Rice, Gillian I. and Consonni, Filippo and Berteloot, Laureline and Largeaud, Laetitia and Conti, Francesca and Roullion, Cécile and Masson, Cécile and Bessot, Boris and Seeleuthner, Yoann and Le Voyer, Tom and Rinchai, Darawan and Rosain, Jérémie and Neehus, Anna-Lena and Erazo-Borrás, Lucia and Li, Hailun and Janda, Zarah and Cho, En-Jui and Muratore, Edoardo and Soudée, Camille and Lainé, Candice and Delabesse, Eric and Goulvestre, Claire and Ma, Cindy S. and Puel, Anne and Tangye, Stuart G. and André, Isabelle and Bole-Feysot, Christine and Abel, Laurent and Erlacher, Miriam and Zhang, Shen-Ying and Béziat, Vivien and Lagresle-Peyrou, Chantal and Six, Emmanuelle and Pasquet, Marlène and Alsina, Laia and Aiuti, Alessandro and Zhang, Peng and Crow, Yanick J. and Landegren, Nils and Masetti, Riccardo and Huang, Danny T. and Casanova, Jean-Laurent and Bustamante, Jacinta (2024) Autoinflammation in patients with leukocytic CBL loss of heterozygosity is caused by constitutive ERK-mediated monocyte activation. Journal of Clinical Investigation, 134 (20): e181604. ISSN 0021-9738
Dearlove, Emily L. and Chatrin, Chatrin and Buetow, Lori and Ahmed, Syed F. and Schmidt, Tobias and Bushell, Martin and Smith, Brian O. and Huang, Danny T. (2024) DTX3L ubiquitin ligase ubiquitinates single-stranded nucleic acids. eLife, 13: RP98070. ISSN 2050-084X
Tobias, Edward S. and Lucas-Herald, Angela K. and Sagar, Danielle and Montezano, Augusto C. and Rios, Francisco J. and De Lucca Camargo, Livia and Hamilton, Graham and Gazdagh, Gabriella and Diver, Louise A. and Williams, Nicola and Herzyk, Pawel and Touyz, Rhian M. and Greenfield, Andy and McGowan, Ruth and Ahmed, S. Faisal (2024) SEC31A may be associated with pituitary hormone deficiency and gonadal dysgenesis. Endocrine, 84. pp. 345-349. ISSN 1355-008X
See full publications listSchmidt, Tobias
Author
Dearlove, Emily L. and Chatrin, Chatrin and Buetow, Lori and Ahmed, Syed F. and Schmidt, Tobias and Bushell, Martin and Smith, Brian O. and Huang, Danny T. (2024) DTX3L ubiquitin ligase ubiquitinates single-stranded nucleic acids. eLife, 13: RP98070. ISSN 2050-084X
See full publications listBushell, Martin
Author
Smith, Brian O.
Author
Dearlove, Emily L. and Chatrin, Chatrin and Buetow, Lori and Ahmed, Syed F. and Schmidt, Tobias and Bushell, Martin and Smith, Brian O. and Huang, Danny T. (2024) DTX3L ubiquitin ligase ubiquitinates single-stranded nucleic acids. eLife, 13: RP98070. ISSN 2050-084X
See full publications listHuang, Danny T.
Author
Vosbein, Pernille and Vergara, Paula Paredes and Huang, Danny T. and Thomson, Andrew R. (2024) An engineered ubiquitin binding coiled coil peptide. Chemical Science, 15 (38). pp. 15776-15782. ISSN 2041-6520
Bohlen, Jonathan and Bagarić, Ivan and Vatovec, Taja and Ogishi, Masato and Ahmed, Syed F. and Cederholm, Axel and Buetow, Lori and Sobrino, Steicy and Le Floc’h, Corentin and Arango-Franco, Carlos A. and Seabra, Luis and Michelet, Marine and Barzaghi, Federica and Leardini, Davide and Saettini, Francesco and Vendemini, Francesca and Baccelli, Francesco and Catala, Albert and Gambineri, Eleonora and Veltroni, Marinella and Aguilar de la Red, Yurena and Rice, Gillian I. and Consonni, Filippo and Berteloot, Laureline and Largeaud, Laetitia and Conti, Francesca and Roullion, Cécile and Masson, Cécile and Bessot, Boris and Seeleuthner, Yoann and Le Voyer, Tom and Rinchai, Darawan and Rosain, Jérémie and Neehus, Anna-Lena and Erazo-Borrás, Lucia and Li, Hailun and Janda, Zarah and Cho, En-Jui and Muratore, Edoardo and Soudée, Camille and Lainé, Candice and Delabesse, Eric and Goulvestre, Claire and Ma, Cindy S. and Puel, Anne and Tangye, Stuart G. and André, Isabelle and Bole-Feysot, Christine and Abel, Laurent and Erlacher, Miriam and Zhang, Shen-Ying and Béziat, Vivien and Lagresle-Peyrou, Chantal and Six, Emmanuelle and Pasquet, Marlène and Alsina, Laia and Aiuti, Alessandro and Zhang, Peng and Crow, Yanick J. and Landegren, Nils and Masetti, Riccardo and Huang, Danny T. and Casanova, Jean-Laurent and Bustamante, Jacinta (2024) Autoinflammation in patients with leukocytic CBL loss of heterozygosity is caused by constitutive ERK-mediated monocyte activation. Journal of Clinical Investigation, 134 (20): e181604. ISSN 0021-9738
Dearlove, Emily L. and Chatrin, Chatrin and Buetow, Lori and Ahmed, Syed F. and Schmidt, Tobias and Bushell, Martin and Smith, Brian O. and Huang, Danny T. (2024) DTX3L ubiquitin ligase ubiquitinates single-stranded nucleic acids. eLife, 13: RP98070. ISSN 2050-084X
See full publications listAvailable under License Creative Commons Attribution.
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