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MBG Focus talk: Beyond recognition: molecular mechanism of FANCD2-FANCI in DNA repair

Pablo Alcon, MRC Laboratory of Molecular Biology, Cambridge

Info about event


Friday 15 March 2024,  at 11:15 - 12:00


Faculty Club (1870-816)

Beyond recognition: molecular mechanism of FANCD2-FANCI in DNA repair

Fanconi Anemia (FA) is a hereditary syndrome caused by a defective ability to repair DNA inter-strand crosslinks (ICLs), which induces genome instability and leads to developmental defects and cancer predisposition. The FA pathway involves the products of at least 23 genes and is crucial for ICL repair. A central step in this pathway is the monoubiquitination of FANCD2-FANCI (D2-I) by the FA core complex. Ubiquitinated D2-I serves as a molecular hub to recruit nucleases for 'unhooking' the lesion. Recently, we showed that D2-I acts as a clamp locked onto DNA by the FA core complex. However, D2-I is also known to play a more general role in DNA repair and in protecting stalled replication forks from unscheduled degradation. The mechanisms underlying DNA damage recognition and the function of D2-I in replication fork protection remain unclear.

In this seminar, I will present our recent work, which combines electron cryo-microscopy (cryoEM) with biochemistry, single-molecule imaging, and other molecular biology techniques to dissect the molecular basis for the activation and regulation of this essential DNA repair pathway.