Interstrand DNA cross-links (ICLs) — chemical bonds that join the two strands of DNA — are a toxic form of DNA damage. ICLs block both replication and transcription, triggering cell death. Drugs that introduce ICLs, such as mitomycin C, are used as chemotherapeutic agents.
ICLs are known to be repaired by a set of proteins that are part of the Fanconi anemia (FA) pathway, but other ICL repair mechanisms are not clear.
Now, Ian Macara, PhD, and colleagues have discovered that a previously uncharacterized protein is a nuclease enzyme that participates in FA-independent ICL repair.
They proposed naming the protein SAN1 (senataxin-associated nuclease 1), based on their finding that it binds to senataxin (SETX). SETX is an enzyme that “unwinds” twisted RNA and DNA loops during transcription.
The findings, reported in Nature Communications, suggest that SAN1 cooperates with SETX in an FA-independent repair process to protect cells from ICLs. The discovery opens new opportunities to understand FA-independent mechanisms of DNA repair for ICLs.
This research was supported by grants from the National Institutes of Health (GM050526, CA197571).
