The DNA damage response pathway is required for multiciliated cell differentiation - PubMed
8 hours ago
- #multiciliated cells
- #DNA damage response
- #centriole amplification
- Multiciliated cells (MCCs) produce hundreds of centrioles in a post-mitotic state, bypassing normal cell cycle constraints.
- During differentiation, MCCs accumulate extensive double-strand DNA breaks, with damage levels scaling with centriole number.
- DNA damage response (DDR) kinases are required for centriole biogenesis and ciliogenesis in MCCs.
- High transcriptional output for centriole and cilia genes generates RNA-DNA hybrids (R-loops) that co-localize with DNA damage sites.
- Transcription-coupled DNA damage engages DDR signaling to permit centriole amplification, rewiring the canonical cell cycle.