Diverse molecular functions of the FA pathway. DNA repair in the FA pathway predominantly restores DNA interstrand cross-links to ensure bona fide replication and transcription. However, this activity is also involved in the resolution of DNA: RNA hybrids known as R-loops occurring predominantly in the nucleolus due to ribosomal DNA transcription by RNA polymerase 1 (RNAP1). R-loop resolution by FANCM, FANCI, and FANCD2 proteins ensures ribosome biogenesis. FANC proteins also clear mitochondria damaged by excessive reactive oxygen species and, in conjunction with PARKIN, execute mitophagy. Ub, ubiquitin modification; FAAP100, FA core complex–associated protein 100.