AP-site

FULL NAME: apurinic/apyrimidinic site


DESCRIPTION:
An AP site (apurinic/apyrimidinic site), also known as an abasic site, is a location in DNA that has neither a purine nor a pyrimidine base, usually due to DNA damage. AP sites can be formed by spontaneous depurination, but also occur as intermediates in base excision repair. In this process, a DNA glycosylase recognizes a damaged base and cleaves the N-glycosidic bond to release the base, leaving an AP site. A variety of glycosylases that recognize different types of damage exist, including oxidized or methylated bases, or uracil in DNA. The AP site can then be cleaved by an AP endonuclease, leaving 3' hydroxyl and 5' deoxyribosephosphate termini (see DNA structure). In alternative fashion, bifunctional glycosylase-lyases can cleave the AP site, leaving a 5' phosphate adjacent to a 3' α,β-unsaturated aldehyde. Both mechanisms form a single-strand break, which is then repaired by either short-patch or long-patch base excision repair. If left unrepaired, AP sites can lead to mutation during semiconservative replication. They can cause replication fork stalling and are bypassed by translesion synthesis. In E. coli, adenine is preferentially inserted across from AP sites, known as the "A rule". The situation is more complex in higher eukaryotes, with different nucleotides showing a preference depending on the organism and experimental conditions.

DAMAGE TYPE: N-glycosidic bond hydrolysis


DNA DAMAGE SOURCE(S) (MAIN):
unstable adducts
repair intermediate


DNA DAMAGE EFFECT(S) (MAIN):
-1 frameshift
cytotoxic
mutagenesis


PATHWAYS:
nucleotide incision repair (NIR)
base excision repair (BER)
nucleotide excision repair (NER)
prokaryotic (SOS) response


DNA repair protein(s) related to damage:
Nfo (endo IV)
APEX1
APEX2
XthA (exo III)
TDP1
UvrC
UvrB
DDB2 (XPE)


Last modification date: Oct. 10, 2011