Literature summary for 4.2.99.B1 extracted from

Quinones, J.L.; Demple, B.
When DNA repair goes wrong BER-generated DNA-protein crosslinks to oxidative lesions (2016), DNA Repair, 44, 103-109 .

Search for more literature for 4.2.99.B1

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P06746	-	-

Synonyms

Synonyms	Comment	Organism
5'-dRP lyase	-	Homo sapiens
pol beta	-	Homo sapiens
PolB	-	Homo sapiens

General Information

General Information	Comment	Organism
malfunction	Detection of stable DNA-protein crosslinks (DPC) between Pol beta and dL in intact cells. Formation of BER-mediated DNA-protein crosslinks, formation of oxidative polbeta-DPC in vivo. Pol beta-DPC are subsequently targeted for ubiquitylation and rapid proteolysis, which is expected to generate 5'-peptidyl-dL-DNA adducts. Inhibition of theproteasome prevents removal of Pol beta-DPC (3B), leading to their toxic accumulation with cell killing and perhaps other consequences. Mitochondrial DNA polymerase gamma (Pol gamma), which harbors a 5'-dRp lyase similar to that of Pol beta, is also trapped by 5'-dL	Homo sapiens
physiological function	oxidized abasic sites are initially incised by Ape1, thus recruiting these lesions into base excision repair (BER) pathways. Lesions such as 2-deoxypentos-4-ulose can be removed by conventional (single-nucleotide) BER, which proceeds through a covalent Schiff base intermediate with DNA polymerase beta (Pol beta) that is resolved by hydrolysis. In contrast, the lesion 2-deoxyribonolactone (dL) must be processed by multinucleotide (long-patch) BER: attempted repair via the single-nucleotide pathway leads to a dead-end, covalent complex with Pol beta cross-linked to the DNA by an amide bond. In classical base excision repair (BER), only the missing nucleotide is replaced by DNA polymerase beta (Pol beta), and the deoxyribose-5'-phosphate (5'-dRp) residue is excised by a 5'-dRp lyase activity in a discrete domain of Pol beta. The result is a nicked DNA that is competent for ligation, usually by DNA ligase III alpha. Another subpathway called long-patch BER (LP-BER) also exists, in which DNA repair synthesis replaces 2-10 nucleotides, Fen1 (flap) endonuclease excises the displaced strand, and DNA ligase I seals the nick. LP-BER repair synthesis can be initiated by Pol beta, which may (inefficiently) insert a second nucleotide. When the 5'-dRp strand is displaced by two or more nucleotides, the 5'-dRp lyase of Pol beta no longer functions, requiring Fen1 to remove the single-stranded flap. BER processing of oxidative DNA damage and the formation of DNA-protein crosslinks (DPC), overview	Homo sapiens

Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.

Release 2023.1 (January 2023)