A round of cell division involves the duplication (‘replication’) of our DNA, followed by the equal distribution of the duplicated chromosomes over two daughter cells during mitosis. To accomplish this, it is essential that the replication of each chromosome is completed, and that all physical connections between the duplicated chromosome arms are removed.
Incomplete DNA replication, which occurs frequently in cancer cells, leads to DNA molecules that remain physically connected during mitosis, preventing proper chromosome segregation. For their survival, tumor cells therefore critically depend on repair mechanisms that resolve these aberrantly connected DNA molecules.
In this study by PhD student Colin Stok, we have identified C1orf112 (now re-named FIRRM) as a regulator of RAD51. FIRRM associates with the AAA+ ATPase FIGNL1, which removes the RAD51 repair protein from chromatin. In the absence of FIRRM or FIGNL1, RAD51 remains aberrantly associated with chromatin, which leads to replication defects and persistently connected chromosomes. As a consequence, inactivation of FIRRM or FIGNL1 in cells leads to defects in mitosis, and a dependance on the mitotic DNA repair factor PICH.
Combined, we have uncovered a new role of the C1orf112 gene, of which the function in human cells was thus far elusive.
For more information, check the link to the article:
FIRRM/C1orf112 is synthetic lethal with PICH and mediates RAD51 dynamics (cell.com)
