Enzymes that protect the immune system may malfunction and provoke cancer-related mutations.
When combatting viruses such as HIV, several enzymes in the immune system may malfunction and cause cancer-related mutations, according to a new study published by Nature Communications.
“Our findings could change the way we treat cancer,” said researcher Linda Chelico, PhD.
The authors discovered that 3 enzymes in the APOBEC3 family trigger these mutations, despite their duties to protect the immune system. These findings may lead to novel inhibitors that suppress the enzymes or tests to determine their levels.
Previous research showed that the enzymes were linked to cancer mutations and may be present in patients with cancer who are not fighting viruses. However, the new study is the first that shows how the enzymes are able to mutate DNA.
“The enzymes we study are very important for building a defence [sic] against viruses, but some specifically activated to fight HIV infection may end up being expressed in the wrong place at the wrong time, causing unintended mutations,” Dr Chelico said.
The authors said that enzymes bind to HIV DNA in order to mutate it and inhibit viral replication, but HIV is notoriously difficult to kill.
Since the enzymes are unable to combat HIV, it continues to scan DNA and may incorrectly cause mutations to healthy cells, according to the study. This process was observed to happen despite the presence of repair mechanisms that protect DNA.
“This is off-target behavior for the enzymes because they typically attack only single-stranded virus DNA,” said researcher Madison Adolph. “We have identified for the first time the biochemical features that allow these enzymes to bind to tiny regions of human DNA that are single-stranded.”
The authors previously attempted to isolate cells from the APOBEC3B enzyme since it was a critical factor in understanding the enzymes, according to the study.
“We were the first research team to study these enzymes outside cells, which is their natural environment,” Adolph said. “We were able to analyze how they cause mutations, instead of looking at already mutated cancer genomes as previous researchers did.”
Although these results are promising, the authors caution that the process that causes the cancer-related mutations is still unknown. The researchers also have yet to determine whether the enzyme mutations cause cancer directly or just increase risk, according to the study.
“We have started a new research phase where we mix healthy cells and these enzymes together in the lab to see what happens, but we are still at a very early stage,” Dr Chelico concluded.