3.5.4.38: single-stranded DNA cytosine deaminase
This is an abbreviated version!
For detailed information about single-stranded DNA cytosine deaminase, go to the full flat file.
Word Map on EC 3.5.4.38
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3.5.4.38
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apobec3s
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deamination
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hypermutation
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deaminases
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immunoglobulin
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uracil
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viruses
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apolipoprotein
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retroviruses
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diversification
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ige
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virion
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polypeptide-like
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retroviral
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mrna-editing
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retrotransposons
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antiretroviral
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retroelements
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vif-deficient
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anti-hiv-1
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retrotransposition
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class-switching
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glycosylase
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lentiviruses
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uracil-dna
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line-1
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proviral
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vif-mediated
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aid-dependent
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cccdna
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aid-induced
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abasic
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c-to-u
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encapsidation
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translesion
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r-loops
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sivmac
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molecular biology
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samhd1
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medicine
- 3.5.4.38
- apobec3s
-
deamination
-
hypermutation
- deaminases
- immunoglobulin
- uracil
- viruses
-
apolipoprotein
- retroviruses
-
diversification
- ige
- virion
-
polypeptide-like
-
retroviral
-
mrna-editing
-
retrotransposons
-
antiretroviral
-
retroelements
-
vif-deficient
-
anti-hiv-1
-
retrotransposition
-
class-switching
- glycosylase
- lentiviruses
-
uracil-dna
-
line-1
-
proviral
-
vif-mediated
-
aid-dependent
-
cccdna
-
aid-induced
-
abasic
-
c-to-u
-
encapsidation
-
translesion
-
r-loops
-
sivmac
- molecular biology
- samhd1
- medicine
Reaction
Synonyms
A3F, activation-induced cytidine deaminase, activation-induced deaminase, AICDA, AID, APOBEC3A, APOBEC3B, APOBEC3C, APOBEC3D, APOBEC3F, APOBEC3G, APOBEC3H, APOBEC3Z1, CDA1, single-stranded (ss)DNA deoxycytidine deaminase, ssDNA cytidine deaminase
ECTree
3.5.4.38 single-stranded DNA cytosine deaminaseAdvanced search results
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results (Substrates Products
Substrates Products on EC 3.5.4.38 - single-stranded DNA cytosine deaminase
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SUBSTRATE 
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
5-methylcytosine in single-stranded DNA + H2O
?
the enzyme exhibits low activity toward 5-methylcytosine n single-stranded DNA
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-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
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-
-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
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-
-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
-
-
-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
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-
-
-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
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-
-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
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-
-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
activation-induced cytidine deaminase (AID) produces DNA breaks in immunoglobulin genes during antibody diversification. Double-stranded breaks in the switch region mediate class switch recombination, and contribute to gene conversion and somatic hypermutation in the variable regions. Among potential highly transcribed genes in mouse hybridoma cells, the immunoglobulin heavy and light chain genes are important AID targets, with the immunoglobulin mu switch region being preferred compared to other genomic sites
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-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
activation-induced deaminase is the initiator for somatic hypermutation (SHM) and class switch recombination (CSR). The enzyme targets the highly repetitive switch regions of the immunoglobulin heavy chain locus to induce DNA double-strand breaks (DSBs), which can be rejoined, leading to switch of constant regions of antibody. When targeting to variable region exons of IgH and IgL loci, the enzyme predominantly induces point mutations, termed SHM, resulting in increased affinity of antibody for antigen. While somatic hypermutation and class switch recombination (CSR) enhance antibody diversity, activation-induced deaminase initiated double-strand breaks and mutations may predispose B cells to carcinogenesis
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-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
AID mediates hypermutation by deaminating single stranded DNA. In vivo, single stranded DNA may arise transiently during transcription
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-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
the enzyme can act on transcribing DNA. It is required for the maturation of antibodies in higher vertebrates, where it promotes somatic hypermutation
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-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
the enzyme deaminates cytidine residues in the DNA of the variable and the switch regions of the immunoglobulin locus. The resulting uracil induces error-prone DNA synthesis in the case of hypermutation or DNA breaks that activate nonhomologous recombination in the case of class-switch recombination
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-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
the enzyme deaminates DNA at transcribed Ig genes. Expressed immunoglobulin genes undergo alterations in sequence and genomic structure in order to optimize antibody function. A single B cell-specific factor, activation-induced deaminase (AID), initiates these changes by deamination of cytosine to uracil. At the Ig loci of B-cells, AID-initiated damage is processed to produce three distinct outcomes: somatic hypermutation, class switch recombination and gene conversion
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-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
the enzyme initiates antibody diversification processes by deaminating immunoglobulin sequences
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?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
activation-induced cytidine deaminase initiates secondary antibody diversification processes by deaminating cytidines on single-stranded DNA. AID preferentially deaminates cytidines preceded by W(A/T)R(A/G) dinucleotides, a sequence specificity that is evolutionarily conserved from bony fish to humans. AID preferentially deaminates bubble substrates of five to seven nucleotides rather than larger bubbles and preferentially binds to bubble-type rather than to single-stranded DNA substrates, suggesting that the natural targets of AID are either transcription bubbles or stem-loop structures. AID displays high affinity for single-stranded DNA. All substrates used in activity assays contain a single cytidine within the bubble and differ in the dinucleotide immediately upstream of the target cytidine constituting either WRC motifs (hot spots) or non-WRC motifs (cold spots)
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-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
among potential highly transcribed genes in mouse hybridoma cells, the immunoglobulin heavy and light chain genes are important targets, with the immunoglobulin mu switch region being preferred compared to other genomic sites
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-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
exclusively catalyses deamination of cytidine in single-stranded DNA. It shows minimal activity on stem-loop structures and preferentially deaminates five-nucleotide bubbles. The optimal target consists of a single-stranded NWRCN motif (W = A or T, R = A or G). WRC preference involves the recognition of a purine in the R position and that the carbonyl or amino side chains of guanosine negatively influence specificity at the W position
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-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
no detectable activity on double-stranded DNA. The enzyme catalyzes deoxycytidine to deoxyuridine deamination activity on double-stranded DNA substrates containing a small transcription-like single-stranded DNA bubble. Enzyme activity depends on sequence context
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-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
the enzyme deaminates cytidine residues in the DNA of the variable and the switch regions of the immunoglobulin locus. The resulting uracil induces error-prone DNA synthesis in the case of hypermutation or DNA breaks that activate nonhomologous recombination in the case of class-switch recombination. The enzyme deaminates single-stranded but not double-stranded substrates unless it is in a complex with replication protein A (RPA) and the substrate is actively undergoing transcription
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-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
the enzyme preferentially deaminates cytosine to uracil in single-stranded and not double-stranded DNA the enzyme deaminates DNA at transcribed Ig genes
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-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
the purified, tetrameric enzyme can deaminate cytidine residues in single-stranded DNA, but not in RNA. It deaminates only single-stranded DNA. Neither cytidine nor CTP (or dCTP) are good substrates for the enzyme in vitro
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-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
conformational equilibrium of the APOBEC3B active site loops, skewed toward being closed, controls enzymatic activity by regulating binding to ssDNA substrates
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?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
the APOBEC3 enzymes are a double-edged sword that can catalyze deamination of cytosine in genomic DNA, which results in potential genomic instability due to the many mutagenic fates of uracil. The enzymes must be able to efficiently deaminate transiently available single-stranded DNA during reverse transcription, replication, or transcription. Specific biochemical characteristics promote deamination in each situation to increase enzyme efficiency through processivity, rapid enzyme cycling between substrates, or oligomerization state
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-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
the APOBEC3 enzymes are a double-edged sword that can catalyze deamination of cytosine in genomic DNA, which results in potential genomic instability due to the many mutagenic fates of uracil. The enzymes must be able to efficiently deaminate transiently available single-stranded DNA during reverse transcription, replication, or transcription. Specific biochemical characteristics promote deamination in each situation to increase enzyme efficiency through processivity, rapid enzyme cycling between substrates, or oligomerization state in DNA
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-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
the enzyme restricts the infectivity of viruses, such as HIV-1, by targeting CCC hotspots scattered through minus DNA strands, reverse-transcribed from genomic RNA
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-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
the enzymes must access single-stranded DNA during the dynamic processes of DNA replication or transcription. The ability of an APOBEC3 to cycle between DNA substrates determines whether it is able to efficiently deaminate single-stranded DNA produced by replication and single-stranded DNA bound by replication protein A. APOBEC3 deaminase activity during transcription has a size limitation that inhibits APOBEC3B tetramers
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-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
deamination activity of methylated cytosine is demonstrated APOBEC3B
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-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
high deaminase activities on cytosine and methylated cytosine with relatively high selectivity for methylated cytosine
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-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
relatively low deaminase activity and selectivity for methylated cytosine
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-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
RNA binding is integral to APOBEC3H function. RNA-mediated dimerization alters the interactions of the enzyme with ssDNA and other RNA molecules
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-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
the enzyme preferentially converts cytidine to uridine at the third position of triplet cytosine (CCC) hotspots. The phosphate backbone is required for C-terminal domain of the enzyme to slide along the DNA strand and to exert the 3'->5' polarity. The higher the salt cncentration, the less prominent is the 3'->5' polarity
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-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
-
-
-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
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-
-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
activation-induced cytidine deaminase (AID) initiates Ig class switch recombination and somatic hypermutation by producing U:G mismatches in DNA. These mismatches also have the potential to induce DNA damage including double-stranded breaks and chromosome translocations
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-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
activation-induced cytidine deaminase (AID) initiates immunoglobulin class switch DNA recombination (CSR) and somatic hypermutation deaminating deoxycytidines in switch and V(D)J region DNA, respectively, to generate deoxyuracils. Processing of deoxyuracils by uracil DNA glycosylase yields abasic sites, which are excised by apurinic/apyrimidinic endonucleases, eventually generating double strand DNA breaks, the obligatory intermediates of class switch DNA recombination
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-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
activation-induced cytidine deaminase (AID) is a mutator enzyme that initiates somatic mutation and class switch recombination in B lymphocytes by introducing uracil:guanine mismatches into DNA. Repair pathways process these mismatches to produce point mutations in the Ig variable region or double-stranded DNA breaks in the switch region DNA. The enzyme can also produce off-target DNA damage, including mutations in oncogenes
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-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
activation-induced deaminase is the initiator for somatic hypermutation (SHM) and class switch recombination (CSR). The enzyme targets the highly repetitive switch regions of the immunoglobulin heavy chain locus to induce DNA double-strand breaks (DSBs), which can be rejoined, leading to switch of constant regions of antibody. When targeting to variable region exons of IgH and IgL loci, the enzyme predominantly induces point mutations, termed SHM, resulting in increased affinity of antibody for antigen. While somatic hypermutation and class switch recombination (CSR) enhance antibody diversity, AID initiated double-strand breaks and mutations may predispose B cells to carcinogenesis
-
-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
in response to antigens, B cells undergo two types of genomic alterations to increase antibody diversity. Affinity for antigen can be increased by introduction of point mutations into immunoglobulin heavy (IgH) and immunoglobulin light (IgL) variable regions by somatic hypermutation. Antibody effector functions can be altered by changing the expressed IgH constant region exons through IgH class switch recombination (CSR). Somatic hypermutation and CSR both require the B-cell-specific activation-induced cytidine deaminase protein (AID), which initiates these reactions through its single-stranded DNA-specific cytidine deaminase activity
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-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
the enzyme induces reproducible DNA breaks at many non-Ig loci in activated B cells
-
-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
the enzyme initiates class switch recombination and somatic hypermutation of immunoglobulin genes in B lymphocytes. Activation-induced cytidine deaminase also produces off-target DNA damage, including mutations in oncogenes and double-stranded breaks that can serve as substrates for oncogenic chromosomal translocations
-
-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
the enzyme initiates Ig heavy chain (IgH) class switch recombination and Ig somatic hypermutation (SHM) by deaminating cytidines within, respectively, IgH switch regions and Ig variable region (V) exons
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-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
the enzyme does neither catalyzes cytidine to uridine editing of apoB mRNA nor binds to AU-rich RNA targets
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-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
unlike AID-induced double-strand DNA breaks in immunoglobulin genes, genome-wide activation-induced cytidine deaminase-dependent double-strand DNA breaks are not restricted to transcribed regions and frequently occur within repeated sequence elements, including CA repeats, non-CA tandem repeats, and short interspersed element
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-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
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-
-
?
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
activation-induced deaminase (AID) is involved in processes leading to antibody diversification: somatic hypermutation, gene conversion, and class-switch recombination
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-
?
additional information
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enzyme is able to deaminate 5-methylcytosine in DNA
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?
additional information
?
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activation-induced cytidine deaminase is function in Pleurodeles waltl. The lack of class switch recombination activity in Pleurodeles waltl is therefore not due to a defect in expression or function of activation-induced cytidine deaminase
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-
?
