spontaneous deamination


DESCRIPTION: Spontaneous deamination is the hydrolysis reaction of cytosine into uracil, releasing ammonia in the process. This can occur in vitro through the use of bisulfite, which converts cytosine, but not 5-methylcytosine. This property has allowed researchers to sequence methylated DNA to distinguish non-methylated cytosine (shown up as uracil) and methylated cytosine (unaltered).

In DNA, this spontaneous deamination is corrected for by the removal of uracil (product of cytosine deamination and not part of DNA) by uracil-DNA glycosylase, generating an abasic (AP) site. The resulting abasic site is then recognised by enzymes (AP endonucleases) that break a phosphodiester bond in the DNA, permitting the repair of the resulting lesion by replacement with another cytosine. A DNA Polymerase may perform this replacement via nick translation, a terminal excision reaction by its 3'-->5' exonuclease activity, followed by a fill-in reaction by its polymerase activity. DNA ligase then forms a phosphodiester bond to seal the resulting nicked duplex product, which now includes a new, correct cytosine.

DNA DAMAGES:
T:5-OH-U pair
5-hydroxy-U (5-OH-U)
dU in dsDNA
dU from U:G
dU in ssDNA
C:5-OH-U pair
hypoxanthine in DNA
A:5-OH-U pair
G:5-OH-U pair
uracil glycol (Ug)
deoxyuridine
cytosine glycol (Cg)
dU from U:A


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NAME STRUCTURE PROTEINS DNA DAMAGE EFFECT(S) PATHWAY(S) RELATED
T:5-OH-U pair mutagenesis
point mutation
T→A transversion
transversion
5-hydroxy-U (5-OH-U) Nth (endo III)
Fpg (MutM)
Ung
Mug
Nei (endo VIII)
SMUG1
NEIL1
NEIL2
NTHL1
no mutagenesis base excision repair (BER)
dU in dsDNA Ung
Mug
C→T transition
mutagenesis
point mutation
substitution
transition
base excision repair (BER)
dU from U:G Mug
Ung
UNG
TDG
SMUG1
mutagenesis
point mutation
substitution
base excision repair (BER)
dU in ssDNA Mug
Ung
UNG
SMUG1
C→T transition
mutagenesis
point mutation
transition
base excision repair (BER)
C:5-OH-U pair mutagenesis
point mutation
hypoxanthine in DNA mutagenesis
point mutation
substitution
A:5-OH-U pair no mutagenesis
G:5-OH-U pair G→A transition
mutagenesis
point mutation
transition
uracil glycol (Ug) Nth (endo III)
Fpg (MutM)
Nth (endo III)
Nei (endo VIII)
mutagenesis
stalled replication fork
base excision repair (BER)
deoxyuridine Ung
Mug
TDG
SMUG1
UNG
AP-site
C→T transition
G→A transition
transition
base excision repair (BER)
cytosine glycol (Cg) NTHL1 C→T transition
transition
base excision repair (BER)
dU from U:A UNG
SMUG1
no mutagenesis base excision repair (BER)

Last modification date: Oct. 5, 2011