JOM KITA KE POLITEKNIK

The DNA-damage kinase ATR activates the FANCD2-FANCI clamp by priming it for ubiquitination (Record no. 1919)

MARC details
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Personal name Sijacki, Tamara
Relator term author
9 (RLIN) 1368
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Title The DNA-damage kinase ATR activates the FANCD2-FANCI clamp by priming it for ubiquitination
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Date of publication, distribution, etc. 2022-09.
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General note /pmc/articles/PMC7613635/
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General note /pubmed/36050501
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Summary, etc. DNA interstrand crosslinks are tumor-inducing lesions that block DNA replication and transcription. When crosslinks are detected at stalled replication forks, ATR kinase phosphorylates FANCI, which stimulates monoubiquitination of the FANCD2-FANCI clamp by the Fanconi anemia (FA) 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-FANCI complexes containing phosphomimetic FANCI. We observe that, unlike wild-type FANCD2-FANCI, the phosphomimetic complex closes around DNA, independent of the FA core complex. Surprisingly, the phosphomimetic mutations do not substantially alter DNA binding but instead destabilize the open state of FANCD2-FANCI and alter its conformational dynamics. Overall, our results reveal that phosphorylation primes the FANCD2-FANCI clamp for ubiquitination, showing how multiple post-translational modifications are coordinated to control DNA-repair.
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Terms governing use and reproduction
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Language note en
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Topical term or geographic name as entry element Article
655 7# - INDEX TERM--GENRE/FORM
Genre/form data or focus term Text
Source of term local
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Alcón, Pablo
Relator term author
9 (RLIN) 1369
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Personal name Chen, Zhuo A.
Relator term author
9 (RLIN) 1370
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Personal name McLaughlin, Stephen H.
Relator term author
9 (RLIN) 1371
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Personal name Shakeel, Shabih
Relator term author
9 (RLIN) 1372
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Personal name Rappsilber, Juri
Relator term author
9 (RLIN) 1373
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Passmore, Lori A.
Relator term author
9 (RLIN) 1374
786 0# - DATA SOURCE ENTRY
Note Nat Struct Mol Biol
856 41 - ELECTRONIC LOCATION AND ACCESS
Uniform Resource Identifier <a href="http://dx.doi.org/10.1038/s41594-022-00820-9">http://dx.doi.org/10.1038/s41594-022-00820-9</a>
Public note Connect to this object online.

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