APOBEC is a group of enzymes that constitute the antiviral “genomic police”. These are enzymes that specialize in recognizing and destroying viral DNA that enters our cells. “APOBECs” bind to single-stranded viral DNA and convert cytosines into uracils, which inactivates the intruder and signals his destruction.

What’s interesting is that retroviruses such as HIV have developed special proteins to disable APOBEC proteins, in order to be able to continue infecting cells. This one of the reasons for such high virulence of HIV. However, APOBEC is not only “good policemen”. Sometimes they do things they shouldn’t. They go crazy and start to … destroy our genome.

This, of course, is not intended. In a situation where the cell’s genome replication “stutters” during mitosis, the cell should die (apoptosis). However, when the mechanisms that control apoptosis fail (e.g., in cancer), the cell is simply stuck in DNA replication, trying to repair the problem. This takes so abnormally long that naked, single-stranded DNA stuck in the replication forks mistakenly attracts APOBEC proteins.

Rather than attacking viral DNA, “APOBECs” begin to bulk convert cytosine to uracil! When replication is resumed, the cell treats the uracils (previously cytosines) as thymine. Hence, where APOBEC was present there is an unprecedented number of mutations of one type: C> T substitution. On the charts of the frequency of variants, it looks like “heavy rain”, hence the phenomenon of this type is named “kataegis”, which in Greek means thunderstorm or downpour.

Wirusy krążące w komórce

Source:

  • https://en.wikipedia.org/wiki/APOBEC3G
  • https://en.wikipedia.org/wiki/Kataegis