(2017) Phosphorylation promotes activation -
induced cytidine deaminase activity at the Myc oncogene.
CRISPR base editing technologies enable the direct conversion of DNA bases (C to T / A / G) without inducing double - strand breaks of DNA by the fusion
of cytidine deaminase with deactivated Cas9 (dCas9) or Cas9 nickase.
They do this by producing a «long form» of an enzyme
called cytidine deaminase.
Bacteria that produce the
enzyme cytidine deaminase converted the drug to an inactive form.
Particular
cytidines in transcripts in chloroplasts and mitochondria of plant cells undergo modification to uridine by RNA editing (1).
The first base editors developed in 2016
use cytidine deaminase to change C - G base pairs to T - A pairs (top).
Examples
include cytidine, uridine, adenosine, guanosine, thymidine and inosine.
(11) This finding supports the idea that DYW domains
carry cytidine deaminase activity.
This domain has been hypothesized to provide the enzymatic activity needed to convert C to U because it carries motifs characteristic
of cytidine deaminases.
The researchers were able to find the bacterial gene responsible for this, a gene
called cytidine deaminase (CDD).
In the process of antibody production, B cells turn on the gene known as activation - induced
cytidine deaminase (AID), which acts as a sort of molecular scissors that cut the chromosomes within the B - cell.
Cytidines or uridines are added to C5 to generate chain lengths of 10 to 11 nucleotides, with longer products being generated at greatly reduced efficiency.
This cellular machinery translates its sequence of four kinds of nucleosides — adenosine,
cytidine, uridine, and guanosine — into a protein.
Fa - Ten Kao, Jinjwei Yu, and their colleagues at the Eleanor Roosevelt Institute for Cancer Research in Denver homed in on a 20 - million - base - pair stretch on the long arm of chromosome 21 called 21q11 - 21, which has a low percentage of
cytidine and guanosine nucleotides — a telltale sign of low gene content, or «junk DNA.»
They found the methylation could be partly reversed by treatment with 5 - aza
cytidine, an analogue of cytidine, resulting in the reactivation of certain transposons.
The analyses revealed a strong preference for
the cytidine and guanosine bases at the ribonucleotide sites.
As these cells rapidly proliferate, they also express high levels of an enzyme known as activation - induced
cytidine deaminase (AID), which induces mutations in their DNA.
In others, they changed pyrimidine RNA nucleotides, with
cytidine or uracil bases, into pyrimidine DNA nucleotides with cytidine or thymidine bases.
Liu and coworkers developed last year's base editor by combining three proteins:
a cytidine deaminase, a natural enzyme that converts C to uridine (U); a mutated Cas9 CRISPR enzyme that doesn't cut DNA but uses an associated guide RNA to target specific DNA sequences; and a protein that prevents reversion of U back to C.
After
the cytidine deaminase changes C to U, the base editor nicks the strand opposite the modification to induce cellular machinery to replace G with A and change U to T.
Dr. Honjo is well known for his discovery of activation - induced
cytidine deaminase that is essential for class switch recombination and somatic hypermutation.
Crystal structure of an ADP - ribosylated protein with
a cytidine deaminase - like fold, but unknown function (TM1506), from Thermotoga maritima at 2.70 A resolution.
Nucleotides:
cytidine 5» - monophosphate, disodium guanosine 5» - monophosphate, disodium uridine 5» - monophosphate, adenosine 5» - monophosphate; 10.