Differential functions of FANCI and FANCD2 ubiquitination stabilize ID2 complex on DNA

Autor: Connor Arkinson, Laura Spagnolo, Mairi Clarke, Helen Walden, Martin L. Rennie, James Streetley, Kimon Lemonidis, Viduth K. Chaugule
Rok vydání: 2020
Předmět:
Conformational change
DNA Repair
DNA repair
Lysine
Biochemistry
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Ubiquitin
Structural Biology
Fanconi anemia
Report
hemic and lymphatic diseases
ubiquitin
FANCD2
Genetics
medicine
Humans
Monoubiquitination
deubiquitination
Molecular Biology
Inhibitor of Differentiation Protein 2
030304 developmental biology
0303 health sciences
biology
Fanconi Anemia Complementation Group D2 Protein
030302 biochemistry & molecular biology
Ubiquitination
DNA Replication
Repair & Recombination
Post-translational Modifications
Proteolysis & Proteomics
DNA
medicine.disease
Fanconi Anemia Complementation Group Proteins
3. Good health
Cell biology
protein–DNA interactions
Fanconi Anemia
chemistry
biology.protein
Fanconi anaemia
030217 neurology & neurosurgery
Reports
DNA Damage
Deubiquitination
Zdroj: EMBO reports
EMBO Reports
ISSN: 1469-221X
DOI: 10.15252/embr.202050133
Popis: The Fanconi anaemia (FA) pathway is a dedicated pathway for the repair of DNA interstrand crosslinks and is additionally activated in response to other forms of replication stress. A key step in the FA pathway is the monoubiquitination of each of the two subunits (FANCI and FANCD2) of the ID2 complex on specific lysine residues. However, the molecular function of these modifications has been unknown for nearly two decades. Here, we find that ubiquitination of FANCD2 acts to increase ID2's affinity for double‐stranded DNA via promoting a large‐scale conformational change in the complex. The resulting complex encircles DNA, by forming a secondary “Arm” ID2 interface. Ubiquitination of FANCI, on the other hand, largely protects the ubiquitin on FANCD2 from USP1‐UAF1 deubiquitination, with key hydrophobic residues of FANCI's ubiquitin being important for this protection. In effect, both of these post‐translational modifications function to stabilize a conformation in which the ID2 complex encircles DNA.
The FANCI‐FANCD2 (ID2) complex is involved in DNA repair. The ubiquitination of each protein acts to maintain the complex on double stranded DNA, but through different mechanisms.
Databáze: OpenAIRE
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