RIF1 Controls Replication Initiation and Homologous Recombination Repair in a Radiation Dose-Dependent Manner
Yuichiro Saito, Junya Kobayashi, Masato T. Kanemaki, Kenshi Komatsu
Journal of Cell Science 2020 May 20. DOI:10.1242/jcs.240036
Genomic DNA is challenged by various types of stresses. Ionizing radiation (IR) cut DNA, generating a DNA damage called a DNA double-strand break (DSB). DSB is repaired via two pathways; an error-prone, ‘non-homologous end joining (NHEJ) pathway’ or a precise, ‘homologous recombination repair (HRR) pathway’. To maintain genome integrity, it is important for cells to choose an appropriate pathway for repairing DSBs.
It is believed that human cells dominantly use error-prone NHEJ to repair DSB. This idea came from the observations using high doses of IR. However, it has not been known whether the predominant use of NHEJ is applicable to DSBs induced by a low dose of IR. To answer this question, we used a low or high dose of IR and monitored the repair pathway. We found that HRR played a prominent role to repair DSBs after a low dose of IR, and it was suppressed after a high dose of IR. These results show that human cells sense radiation dose and choose an appropriate repair pathway. Furthermore, we identified RIF1 as a critical factor that controls HRR activity in an IR-dose dependent manner. We expect that these results would provide basic understandings of how radiation kills cancer cells in radiation therapy.
Figure: DNA double-strand break is repaired via the non-homologous end joining (NHEJ) or homologous recombination repair (HRR) pathway. RIF1 suppresses HRR only after a high dose of IR, directing cells towards using the NHEJ pathway.