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Updated: Jun 10, 2026

Advanced Confocal Microscopy Techniques to Study Protein-protein Interactions and Kinetics at DNA Lesions
Published on: November 12, 2017
The FANCM/FAAP24 complex is required for the DNA interstrand crosslink-induced checkpoint response
Min Huang1, Jung Min Kim, Bunsyo Shiotani
1Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
None:
Cells from Fanconi anemia (FA) patients are extremely sensitive to DNA interstrand crosslinking (ICL) agents, but the molecular basis of the hypersensitivity remains to be explored. FANCM (FA complementation group M), and its binding partner, FAAP24, anchor the multisubunit FA core complex to chromatin after DNA damage and may contribute to ICL-specific cellular response. Here we show that the FANCM/FAAP24 complex is specifically required for the recruitment of replication protein A (RPA) to ICL-stalled replication forks. ICL-induced RPA foci formation requires the DNA-binding activity of FAAP24 but not the DNA translocase activity of FANCM. Furthermore, FANCM/FAAP24-dependent RPA foci formation is required for efficient ATR-mediated checkpoint activation in response to ICL. Therefore, we propose that FANCM/FAAP24 plays a role in ICL-induced checkpoint activation through regulating RPA recruiment at ICL-stalled replication forks.
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