A team of Swiss and Russian scientists has decoded how a defence protein that fights viral infections in our body takes advantage of a weakness in our DNA replication process to induce mutations in our genome, leading to cancer.The defence protein called “APOBEC” is a useful yet dangerous, intrinsic cellular protein. The researchers have observed that mutations induced by APOBEC can be found in many tumourous cells throughout the genome. How can APOBEC - which can affect only single-stranded DNA - be the cause of so many cancers in human beings? “We were very surprised to observe that in APOBEC cancers, the mutation rate is equally distributed in all regions. When APOBEC is involved, mutations occur early during replication, and affect important genes,” explained Vladimir Seplyarskiy from the Russian Academy of Sciences and fist author of this study.
These mutations tend to be more deleterious than other kind of mutations, Seplyarskiy added.Since the scientists knew that APOBEC can only mutate single stranded DNA, they needed to identify in what direction the replication fork was going in order to identify the DNA regions that stay single-stranded for longer period of time.“For the first time ever, we managed to do so in human cells. We were able to identify the direction of the replication fork for about 20 percent of the genome, and found twice as many mutations,” informed Sergey Nikolaev, geneticist at University of Geneva (UNIGE), Switzerland, in a paper appeared in the journal Genome Research.The scientists will continue their research to better understand how tumorous cells replicate their DNA differently from healthy cells.