“Microhomology-mediated end joining acts directly on replication forks to repair single-ended double strand breaks,” is now available online!
When cells divide, they must copy their DNA so that the divided cells each receive a complete set of genetic instructions. During this process, the DNA-copying mechanisms can stall or break under what is called “replication stress,” which is common in cancer cells. These breaks, however, can be repaired so that the cell survives.
In this study, the Gilbert lab contributes to a larger effort as the researchers collaborate to examine that repair process called microhomology-mediated end joining (MMEJ). The researchers found that this repair pathway can act directly at the broken replication fork, working alongside another repair mechanism known as break-induced replication (BIR).
They also discovered that a protein called Polθ helps carry out this repair, while another key DNA damage response protein, ATR, can suppress it and instead promote the BIR pathway.
Importantly, the study found that blocking both ATR and Polθ at the same time strongly kills cancer cells experiencing high replication stress, while having much less effect on normal cells. This suggests a potential new strategy for developing targeted cancer therapies.
Great work by San Diego BioMed’s Gilbert lab and the whole team! We look forward to their continued discoveries!