dctpdeaminase.md

title: dCTPdeaminase
layout: article
tableColumns:
    article:
      doi: 10.1038/s41564-022-01158-0
      abstract: |
        DNA viruses and retroviruses consume large quantities of deoxynucleotides (dNTPs) when replicating. The human antiviral factor SAMHD1 takes advantage of this vulnerability in the viral lifecycle, and inhibits viral replication by degrading dNTPs into their constituent deoxynucleosides and inorganic phosphate. Here, we report that bacteria use a similar strategy to defend against bacteriophage infection. We identify a family of defensive bacterial deoxycytidine triphosphate (dCTP) deaminase proteins that convert dCTP into deoxyuracil nucleotides in response to phage infection. We also identify a family of phage resistance genes that encode deoxyguanosine triphosphatase (dGTPase) enzymes, which degrade dGTP into phosphate-free deoxyguanosine and are distant homologues of human SAMHD1. Our results suggest that bacterial defensive proteins deplete specific deoxynucleotides (either dCTP or dGTP) from the nucleotide pool during phage infection, thus starving the phage of an essential DNA building block and halting its replication. Our study shows that manipulation of the dNTP pool is a potent antiviral strategy shared by both prokaryotes and eukaryotes..
    Sensor: Host integrity monitoring
    Activator: Unknown
    Effector: Nucleotide modifying
    PFAM: PF00383, PF14437
contributors:
    - Nathalie Bechon
relevantAbstracts:
    - doi: 10.1038/s41564-022-01162-4
    - doi: 10.1038/s41564-022-01158-0


# dCTPdeaminase
## Description
dCTPdeaminase is a family of systems. dCTPdeaminase from Escherichia coli has been shown to provide resistance against various lytic phages when expressed heterologously in another Escherichia coli by degrading the pool of dCTP available for phage DNA replication.
This system is mostly found in Proteobacteria but a few examples also exist in Acidobacteria, Actinobacteria, Bacteroidetes, Cyanobacteria, Firmicutes, Planctomyces, and Verrucomicrobia.
Those systems can be found in plasmids (around 8%).

## Mechanism
When activated by a phage infection, dCTPdeaminase, will convert deoxycytidine (dCTP/dCDP/dCMP) into deoxyuridine.
This action will deplete the pool of CTP nucleotide necessary for the phage replication and will stop the infection.
The trigger for dCTPdeaminase may be linked to the shutoff of RNAP ($\sigma$ S-dependent host RNA polymerase) that occur during phage infections.

## Example of genomic structure

The dCTPdeaminase system is composed of one protein: dCTPdeaminase.

Here is an example found in the RefSeq database:

![dctpdeaminase](/dctpdeaminase/dCTPdeaminase.svg){max-width=750px}

dCTPdeaminase system in the genome of *Vibrio parahaemolyticus* (GCF_009883855.1) is composed of 1 protein: dCTPdeaminase (WP_029845369.1).

## Distribution of the system among prokaryotes

The dCTPdeaminase system is present in a total of 269 different species.

Among the 22k complete genomes of RefSeq, this system is present in 501 genomes (2.2 %).

![dctpdeaminase](/dctpdeaminase/Distribution_dCTPdeaminase.svg){max-width=750px}

*Proportion of genome encoding the dCTPdeaminase system for the 14 phyla with more than 50 genomes in the RefSeq database.*

## Structure

### dCTPdeaminase

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