Microarray screening reveals two non-conventional SUMO-binding modules linked to DNA repair by non-homologous end-joiningCitation formats

  • External authors:
  • Matthew Jenner
  • Metztli Cisneros-Aguirre
  • Kira Brüninghoff
  • Christian M. Loch
  • Stephen P Jackson
  • Qian Wu
  • Henning D. Mootz
  • Jeremy M. Stark
  • Christine Schmidt

Standard

Microarray screening reveals two non-conventional SUMO-binding modules linked to DNA repair by non-homologous end-joining. / Cabello Lobato, Maria Jose; Jenner, Matthew; Cisneros-Aguirre, Metztli; Brüninghoff, Kira; Sandy, Zac; Da Costa, Isabelle Cristine; Jowitt, Thomas; Loch, Christian M.; Jackson , Stephen P ; Wu, Qian; Mootz, Henning D.; Stark, Jeremy M.; Cliff, Matthew; Schmidt, Christine.

In: Nucleic acids research, 22.03.2022.

Research output: Contribution to journalArticlepeer-review

Harvard

Cabello Lobato, MJ, Jenner, M, Cisneros-Aguirre, M, Brüninghoff, K, Sandy, Z, Da Costa, IC, Jowitt, T, Loch, CM, Jackson , SP, Wu, Q, Mootz, HD, Stark, JM, Cliff, M & Schmidt, C 2022, 'Microarray screening reveals two non-conventional SUMO-binding modules linked to DNA repair by non-homologous end-joining', Nucleic acids research.

APA

Cabello Lobato, M. J., Jenner, M., Cisneros-Aguirre, M., Brüninghoff, K., Sandy, Z., Da Costa, I. C., Jowitt, T., Loch, C. M., Jackson , S. P., Wu, Q., Mootz, H. D., Stark, J. M., Cliff, M., & Schmidt, C. (Accepted/In press). Microarray screening reveals two non-conventional SUMO-binding modules linked to DNA repair by non-homologous end-joining. Nucleic acids research.

Vancouver

Author

Cabello Lobato, Maria Jose ; Jenner, Matthew ; Cisneros-Aguirre, Metztli ; Brüninghoff, Kira ; Sandy, Zac ; Da Costa, Isabelle Cristine ; Jowitt, Thomas ; Loch, Christian M. ; Jackson , Stephen P ; Wu, Qian ; Mootz, Henning D. ; Stark, Jeremy M. ; Cliff, Matthew ; Schmidt, Christine. / Microarray screening reveals two non-conventional SUMO-binding modules linked to DNA repair by non-homologous end-joining. In: Nucleic acids research. 2022.

Bibtex

@article{3f2d9d86217c4ed9993a2e5ba5873faa,
title = "Microarray screening reveals two non-conventional SUMO-binding modules linked to DNA repair by non-homologous end-joining",
abstract = "SUMOylation is critical for numerous cellular signalling pathways, including the maintenance of genome integrity via the repair of DNA double-strand breaks (DSBs). If misrepaired, DSBs can lead to cancer, neurodegeneration, immunodeficiency and premature ageing. Using systematic human proteome microarray screening combined with widely applicable carbene footprinting, genetic code expansion and high-resolution structural profiling, we define two non-conventional and topologyselective SUMO2-binding regions on XRCC4, a DNA repair protein important for DSB repair by nonhomologous end-joining (NHEJ). Mechanistically, the interaction of SUMO2 and XRCC4 is incompatible with XRCC4 binding to three other proteins important for NHEJ-mediated DSB repair. These findings are consistent with SUMO2 forming a redundant NHEJ layer with the potential to regulate different NHEJ complexes at distinct levels including, but not limited to, XRCC4 interactions with XLF, LIG4 and IFFO1. Regulation of NHEJ is not only relevant for carcinogenesis, but also for the design of precision anti-cancer medicines and the optimisation of CRISPR/Cas9-based gene editing. In addition to providing molecular insights into NHEJ, this work uncovers a conserved SUMObinding module and provides a rich resource on direct SUMO binders exploitable towards uncovering SUMOylation pathways in a wide array of cellular processes.",
author = "{Cabello Lobato}, {Maria Jose} and Matthew Jenner and Metztli Cisneros-Aguirre and Kira Br{\"u}ninghoff and Zac Sandy and {Da Costa}, {Isabelle Cristine} and Thomas Jowitt and Loch, {Christian M.} and Jackson, {Stephen P} and Qian Wu and Mootz, {Henning D.} and Stark, {Jeremy M.} and Matthew Cliff and Christine Schmidt",
year = "2022",
month = mar,
day = "22",
language = "English",
journal = "Nucleic acids research",
issn = "0305-1048",
publisher = "Oxford University Press",

}

RIS

TY - JOUR

T1 - Microarray screening reveals two non-conventional SUMO-binding modules linked to DNA repair by non-homologous end-joining

AU - Cabello Lobato, Maria Jose

AU - Jenner, Matthew

AU - Cisneros-Aguirre, Metztli

AU - Brüninghoff, Kira

AU - Sandy, Zac

AU - Da Costa, Isabelle Cristine

AU - Jowitt, Thomas

AU - Loch, Christian M.

AU - Jackson , Stephen P

AU - Wu, Qian

AU - Mootz, Henning D.

AU - Stark, Jeremy M.

AU - Cliff, Matthew

AU - Schmidt, Christine

PY - 2022/3/22

Y1 - 2022/3/22

N2 - SUMOylation is critical for numerous cellular signalling pathways, including the maintenance of genome integrity via the repair of DNA double-strand breaks (DSBs). If misrepaired, DSBs can lead to cancer, neurodegeneration, immunodeficiency and premature ageing. Using systematic human proteome microarray screening combined with widely applicable carbene footprinting, genetic code expansion and high-resolution structural profiling, we define two non-conventional and topologyselective SUMO2-binding regions on XRCC4, a DNA repair protein important for DSB repair by nonhomologous end-joining (NHEJ). Mechanistically, the interaction of SUMO2 and XRCC4 is incompatible with XRCC4 binding to three other proteins important for NHEJ-mediated DSB repair. These findings are consistent with SUMO2 forming a redundant NHEJ layer with the potential to regulate different NHEJ complexes at distinct levels including, but not limited to, XRCC4 interactions with XLF, LIG4 and IFFO1. Regulation of NHEJ is not only relevant for carcinogenesis, but also for the design of precision anti-cancer medicines and the optimisation of CRISPR/Cas9-based gene editing. In addition to providing molecular insights into NHEJ, this work uncovers a conserved SUMObinding module and provides a rich resource on direct SUMO binders exploitable towards uncovering SUMOylation pathways in a wide array of cellular processes.

AB - SUMOylation is critical for numerous cellular signalling pathways, including the maintenance of genome integrity via the repair of DNA double-strand breaks (DSBs). If misrepaired, DSBs can lead to cancer, neurodegeneration, immunodeficiency and premature ageing. Using systematic human proteome microarray screening combined with widely applicable carbene footprinting, genetic code expansion and high-resolution structural profiling, we define two non-conventional and topologyselective SUMO2-binding regions on XRCC4, a DNA repair protein important for DSB repair by nonhomologous end-joining (NHEJ). Mechanistically, the interaction of SUMO2 and XRCC4 is incompatible with XRCC4 binding to three other proteins important for NHEJ-mediated DSB repair. These findings are consistent with SUMO2 forming a redundant NHEJ layer with the potential to regulate different NHEJ complexes at distinct levels including, but not limited to, XRCC4 interactions with XLF, LIG4 and IFFO1. Regulation of NHEJ is not only relevant for carcinogenesis, but also for the design of precision anti-cancer medicines and the optimisation of CRISPR/Cas9-based gene editing. In addition to providing molecular insights into NHEJ, this work uncovers a conserved SUMObinding module and provides a rich resource on direct SUMO binders exploitable towards uncovering SUMOylation pathways in a wide array of cellular processes.

M3 - Article

JO - Nucleic acids research

JF - Nucleic acids research

SN - 0305-1048

ER -