MAD2L2 dimerization and TRIP13 control shieldin activity in DNA repair

Inge Krijger, Bastian Föhr, Santiago Hernández Pérez, Estelle Vincendeau, Judit Serrat, Alexander Marc Thouin, Vivek Susvirkar, Chloé Lescale, Inés Paniagua, Liesbeth Hoekman, Simranjeet Kaur, Maarten Altelaar, Ludovic Deriano, Alex C. Faesen and Jacqueline J. L. Jacobs ()
Additional contact information
Inge Krijger: The Netherlands Cancer Institute
Bastian Föhr: Max-Planck Institute for Biophysical Chemistry
Santiago Hernández Pérez: The Netherlands Cancer Institute
Estelle Vincendeau: INSERM U1223, Institut Pasteur
Judit Serrat: The Netherlands Cancer Institute
Alexander Marc Thouin: The Netherlands Cancer Institute
Vivek Susvirkar: Max-Planck Institute for Biophysical Chemistry
Chloé Lescale: INSERM U1223, Institut Pasteur
Inés Paniagua: The Netherlands Cancer Institute
Liesbeth Hoekman: The Netherlands Cancer Institute
Simranjeet Kaur: Max-Planck Institute for Biophysical Chemistry
Maarten Altelaar: The Netherlands Cancer Institute
Ludovic Deriano: INSERM U1223, Institut Pasteur
Alex C. Faesen: Max-Planck Institute for Biophysical Chemistry
Jacqueline J. L. Jacobs: The Netherlands Cancer Institute

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract MAD2L2 (REV7) plays an important role in DNA double-strand break repair. As a member of the shieldin complex, consisting of MAD2L2, SHLD1, SHLD2 and SHLD3, it controls DNA repair pathway choice by counteracting DNA end-resection. Here we investigated the requirements for shieldin complex assembly and activity. Besides a dimerization-surface, HORMA-domain protein MAD2L2 has the extraordinary ability to wrap its C-terminus around SHLD3, likely creating a very stable complex. We show that appropriate function of MAD2L2 within shieldin requires its dimerization, mediated by SHLD2 and accelerating MAD2L2-SHLD3 interaction. Dimerization-defective MAD2L2 impairs shieldin assembly and fails to promote NHEJ. Moreover, MAD2L2 dimerization, along with the presence of SHLD3, allows shieldin to interact with the TRIP13 ATPase, known to drive topological switches in HORMA-domain proteins. We find that appropriate levels of TRIP13 are important for proper shieldin (dis)assembly and activity in DNA repair. Together our data provide important insights in the dependencies for shieldin activity.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-25724-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25724-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-25724-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().