Biology

Dr. María Moriel-Carretero
Institute of Human Genetics, CNRS, Montpellier, France

Fanconi anemia (FA) is a multi-system hereditary disorder caused by mutations in one of 20 FA genes. The disease manifests with congenital abnormalities, exhaustion of the pool of hematopoietic stem cells and cancer proneness. FA proteins exert a variety of functions in cellular stress responses that range from the protection against replication-associated genomic instability and the repair of inter-strand DNA crosslinks to antiviral responses and mitophagy. Recently, it has been found that FA cells are prone to chromosomal instability caused by transcription-associated RNA-DNA hybrids, which are thought to challenge the progression of replication forks. In line with the relationship of FA proteins and the metabolism of transcription, we find that FA proteins FANCD2 and FANCI associate with SF3B1, a key component of the spliceosomal U2 ribonucleoparticle. We report that they modulate the redistribution of prototypal splicing factors in space and time: between speckles and chromatin, during interphase and mitosis, as well as both in basal or in genotoxic conditions. Our findings thus reveal a fundamental context in the metabolism of transcription which helps understand their contribution to genome stability.