PS00727

AP endonucleases family 1 signature 2

PROSITE patterns entry
Member databasePROSITE patterns
PROSITE patterns typeconserved site
Short nameAP_NUCLEASE_F1_2

Description

Cellular DNA is spontaneously and continuously damaged by environmental and internal factors such as X-rays, UV light and agents such as the antitumor drugs bleomycin and neocarzinostatin or those that generate oxygen radicals. Apurinic/apyrimidinic (AP) sites form both spontaneously and as highly cytotoxic intermediates in the removal of the damaged base by the base excision repair (BER) pathway. DNA repair at the AP sites is initiated by specific endonuclease cleavage of the phosphodiester backbone. Such endonucleases are also generally capable of removing blocking groups from the 3'terminus of DNA strand breaks. AP endonucleases can be classified into two families on the basis of sequence similarity and structure (cf. family 2 {PDOC00599}). What we call family 1 groups the enzymes listed below
[1]
. - Escherichia coli exonuclease III (gene xthA) (EC 3.1.11.2). - Streptococcus pneumoniae and Bacillus subtilis exonuclease A (gene exoA) (EC=3.1.11.2). - Mammalian AP endonuclease 1 (AP1) (EC 4.2.99.18). - Drosophila recombination repair protein 1 (gene Rrp1) (EC=4.2.99.18). - Arabidopsis thaliana apurinic endonuclease-redox protein (gene arp) (EC=4.2.99.18). - Dictyostelium DNA-(apurinic or apyrimidinic site) lyase (gene apeA) (EC=4.2.99.18). Except for Rrp1 and arp, these enzymes are proteins of about 300 amino-acid residues. Rrp1 and arp both contain additional and unrelated sequences in their N-terminal section (about 400 residues for Rrp1 and 270 for arp). The structures of bacterial exonuclease III and mammalian AP endonuclease 1 show an alpha/beta-sandwich structure with a fold similar to that of DNase I. One or two divalent metal ions such as magnesium or manganese can bind in the active site
[4]
. We developed three signature patterns and a profile for this family of enzymes. The first pattern contains a glutamate which has been shown
[3]
, in the Escherichia coli enzyme to bind a divalent metal ion such as magnesium or manganese. The patterns are based on the most conserved regions
[2]
. We also developed a profile that spans the entire AP endonucleases family 1 structure.

References

1.Structure and function of apurinic/apyrimidinic endonucleases. Barzilay G, Hickson ID. Bioessays 17, 713-9, (1995). View articlePMID: 7661852

2.Role of the tryptophan residue in the vicinity of the catalytic center of exonuclease III family AP endonucleases: AP site recognition mechanism. Kaneda K, Sekiguchi J, Shida T. Nucleic Acids Res 34, 1552-63, (2006). PMID: 16540594

3.Structure and function of the multifunctional DNA-repair enzyme exonuclease III. Mol CD, Kuo CF, Thayer MM, Cunningham RP, Tainer JA. Nature 374, 381-6, (1995). View articlePMID: 7885481

4.Two divalent metal ions in the active site of a new crystal form of human apurinic/apyrimidinic endonuclease, Ape1: implications for the catalytic mechanism. Beernink PT, Segelke BW, Hadi MZ, Erzberger JP, Wilson DM 3rd, Rupp B. J. Mol. Biol. 307, 1023-34, (2001). View articlePMID: 11286553

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