PXD026912 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | MAD2L2 dimerization and TRIP13 control shieldin activity in DNA repair |
Description | MAD2L2 (also known as REV7) functions in a diverse range of processes. It facilitates DNA lesion bypass through translesion synthesis (TLS), aids in interstrand crosslink repair and contributes to timely mitotic progression. Moreover, MAD2L2 plays an important role in DNA repair at DNA double strand breaks (DSBs) and uncapped telomeres. As the first identified member of the shieldin complex, consisting of MAD2L2, SHLD1, SHLD2 and SHLD3, it controls DNA repair pathway choice between non-homologous end-joining (NHEJ) and homologous recombination (HR) by counteracting DNA end-resection. Here we investigated the requirements for shieldin complex assembly and activity. Besides a dimerization surface, HORMA domain containing protein MAD2L2 has the extraordinary ability to wrap its C-terminal tail around an interacting peptide motif in SHLD3, thereby likely creating a very stable complex. We show that appropriate function of MAD2L2 in DNA repair as a member of the shieldin complex requires it to form a dimer that is mediated by SHLD2 and accelerates MAD2L2-SHLD3 interaction. Dimerization defective MAD2L2 impairs assembly of shieldin and fails to promote NHEJ at telomeres and during immunoglobulin class switch recombination (CSR). Moreover, dimerization of MAD2L2, along with the presence of SHLD3, allows the shieldin complex to interact with the AAA+ family ATPase TRIP13, 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. |
HostingRepository | PRIDE |
AnnounceDate | 2021-09-21 |
AnnouncementXML | Submission_2021-09-21_01:35:55.240.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Liesbeth Hoekman |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2021-06-24 08:22:38 | ID requested | |
⏵ 1 | 2021-09-21 01:35:55 | announced | |
2 | 2021-09-21 01:54:45 | announced | 2021-09-21: Updated project metadata. |
Publication List
Keyword List
submitter keyword: MAD2L2, DNA repair, shieldin, NHEJ, TRIP13 |
Contact List
Maarten Altelaar |
contact affiliation | Proteomics Facility, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands Biomolecular Mass Spectrometry and Proteomics, Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Padualaan 8, 3584 CH Utrecht, The Netherlands |
contact email | m.altelaar@nki.nl |
lab head | |
Liesbeth Hoekman |
contact affiliation | The Netherlands Cancer Institute, Amsterdam, The Netherlands. |
contact email | l.hoekman@nki.nl |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD026912
- Label: PRIDE project
- Name: MAD2L2 dimerization and TRIP13 control shieldin activity in DNA repair