Literature summary for 4.2.99.18 extracted from

Beaver, J.M.; Lai, Y.; Xu, M.; Casin, A.H.; Laverde, E.E.; Liu, Y.
AP endonuclease 1 prevents trinucleotide repeat expansion via a novel mechanism during base excision repair (2015), Nucleic Acids Res., 43, 5948-5960 .

Search for more literature for 4.2.99.18

Cloned(Commentary)

Cloned (Comment)	Organism
gene APE1, recombinant expression of the enzyme in Escherichia coli strain Rosetta II(DE3)	Homo sapiens

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Mg2+	required	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
additional information	Homo sapiens	APE1 promotes the removal of a TNR hairpin during BER of a base lesion in the hairpin loop region. This is accomplished by the 3'-5'-exonuclease activity of the enzyme that cleaved the upstream 3'-region exonucleolytically, resolving the double-flap intermediate and preventing TNR expansions. APE1 significantly stimulates the ligation activity of LIG I to specifically facilitate the completion of hairpin removal. This is the first evidence of APE1 preventing TNR expansions by facilitating hairpin removal	?	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P27695	-	-

Purification (Commentary)

Purification (Comment)	Organism
recombinant enzyme from Escherichia coli strain Rosetta II(DE3) by anion exchange chromatography, dialysis, cation exchange chromatography, dialysis, and hydrophobic interaction chromatography	Homo sapiens

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
additional information	APE1 promotes the removal of a TNR hairpin during BER of a base lesion in the hairpin loop region. This is accomplished by the 3'-5'-exonuclease activity of the enzyme that cleaved the upstream 3'-region exonucleolytically, resolving the double-flap intermediate and preventing TNR expansions. APE1 significantly stimulates the ligation activity of LIG I to specifically facilitate the completion of hairpin removal. This is the first evidence of APE1 preventing TNR expansions by facilitating hairpin removal	Homo sapiens	?	-	?
additional information	substrates are DNA oligonucleotides which contain an 8-oxoguanine (8-oxoG). APE1 fails to directly stimulate FEN1 cleavage on a double-flap intermediate. APE1 promotes the production of the unexpanded repair product by stimulating LIG I	Homo sapiens	?	-	?

Synonyms

Synonyms	Comment	Organism
AP endonuclease 1	-	Homo sapiens
APE1	-	Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C]	Temperature Optimum Maximum [°C]	Comment	Organism
37	-	assay at	Homo sapiens

pH Optimum

pH Optimum Minimum	pH Optimum Maximum	Comment	Organism
7.5	-	assay at	Homo sapiens

General Information

General Information	Comment	Organism
physiological function	AP endonuclease 1 (APE1) is a multifunctional protein abundant in human cells that is essential in maintaining multiple cellular functions. AP endonuclease 1 (APE1) takes part in the base excision repair (BER). It prevents trinucleotide repeat (TNR) expansions via its 3'-5'-exonuclease activity and stimulatory effect on DNA ligation during BER in a hairpin loop. Coordinating with flap endonuclease 1, the APE1 3'-5'-exonuclease activity cleaves the annealed upstream 3'-flap of a double-flap intermediate resulting from 5'-incision of an abasic site in the hairpin loop. Furthermore, APE1 stimulates DNA ligase I to resolve a long double-flap intermediate, thereby promoting hairpin removal and preventing TNR expansions	Homo sapiens

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Release 2023.1 (January 2023)