FANCD2-FANCI surveys DNA and recognizes double- to single-stranded junctions

Duration

45 min

Collaborators

Professor David Rueda, Imperial College London and MRC - Laboratory of Medical Sciences

DNA crosslinks block DNA replication and are repaired by the Fanconi Anemia pathway. The FANCD2-FANCI (D2-I) protein complex is central to this process as it initiates repair and is also known to play a more general role in DNA repair and in protecting stalled replication forks from unscheduled degradation.

Here, using single-molecule imaging, we investigate the behaivior of D2-I and provide a unified molecular mechanism that reconciles the roles of D2-I in recognition and protection of stalled replication forks in multiple DNA repair pathways.

Key learning points:

● The molecular dynamics by which FANCD2-FANCI recognizes DNA damage

● The impact on replication fork protection in bone marrow homeostasis and cancer development

● How dynamic single molecule microscopy was used to generate the key data