Proteomics

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Crosslinking/mass spectrometry analysis of Fanconi anemia (FA) pathway FANCD2-FANCI complexes


ABSTRACT: DNA interstrand crosslinks (ICLs) are repaired by the Fanconi anemia (FA) pathway. The FA pathway is activated by phosphorylation of FANCI in FANCD2-FANCI complex. To investigate how phosphorylation regulates FA pathway activation and function, recombinant FANCD2-FANCI complexes prepared using either the wild-type FANCI or the phosphomimetic FANCI, were comparied using crosslinking/mass spectrometry.

ORGANISM(S): Cellular Organisms

SUBMITTER: Juri Rappsilber 

PROVIDER: PXD031632 | JPOST Repository | Fri Nov 18 00:00:00 GMT 2022

REPOSITORIES: jPOST

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Publications

The DNA-damage kinase ATR activates the FANCD2-FANCI clamp by priming it for ubiquitination.

Sijacki Tamara T   Alcón Pablo P   Chen Zhuo A ZA   McLaughlin Stephen H SH   Shakeel Shabih S   Rappsilber Juri J   Passmore Lori A LA  

Nature structural & molecular biology 20220901 9


DNA interstrand cross-links are tumor-inducing lesions that block DNA replication and transcription. When cross-links are detected at stalled replication forks, ATR kinase phosphorylates FANCI, which stimulates monoubiquitination of the FANCD2-FANCI clamp by the Fanconi anemia core complex. Monoubiquitinated FANCD2-FANCI is locked onto DNA and recruits nucleases that mediate DNA repair. However, it remains unclear how phosphorylation activates this pathway. Here, we report structures of FANCD2-F  ...[more]

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