Role of RNA:DNA hybrids management in controlling mitotic chromosome structure in human cancer cells

R-loops are three-stranded nucleic acid structures that contain RNA paired with its antisense DNA template and a loop of displaced single-stranded DNA (ssDNA). RNA-DNA hybrids formation occurs in a natural context and has been demonstrated to critically impact on epigenetic gene regulation. However, persistent RNA:DNA hybrids have been shown to cause replication stress, chromosome fragility, mitotic defects, and chromosome rearrangements. We found that the RNA-binding protein SFPQ has a critical role in maintaining genome stability by resolving RNA:DNA hybrids at telomeres of vertebrate cells. Starting from this work, we found that SFPQ function is not limited to telomeres but has a critical role in stabilizing repeat rich regions across genome including pericentric regions. Loss of SFPQ alters cell cycle progression and triggers mitotic defects such as chromatin bridges and multilobed cells. We found that SFPQ has a role in preventing sister chromatid exchange, aberrant chromosome architecture and altered sister chromatid cohesion. Our data suggest an involvement of SFPQ and RNA:DNA hybrids in controlling mitotic chromosome structures and faithful chromosome segregation in mitosis. Together, our results indicate a role for SFPQ as important regulator of RNA:DNA hybrid related genomic instability.