RHINO, the protein encoded by the RHNO1 gene, has a previously unknown function in repairing DNA damage. A study recently published in Science demonstrates that RHINO plays a crucial role in a DNA damage repair mechanism called microhomology-mediated end joining (MMEJ) during mitosis.

MMEJ is a pathway used by cells to repair DNA double-strand breaks which involves short homologous sequences on either side of a lesion. The exact details of MMEJ have not been fully understood so far. It has been believed that MMEJ serves as a backup for the two major DNA repair mechanisms, non-homologous end-joining (NHEJ) and homologous recombination (HR). These pathways act during specific phases of the cell cycle and are repressed during mitosis.

For their investigations, the researchers used cells which lacked NHEJ and HR and thus depended on MMEJ for mending DNA double-strand breaks. Knockout of genes by CRISPR/Cas9 allowed them to identify the essential factors required for MMEJ. They also showed that RHINO is predominantly expressed during mitosis and promotes recruitment of DNA polymerase theta, thus enabling the repair of DNA damage originating in previous cell cycle stages.