Page last updated: 2024-10-24

5'-tyrosyl-DNA phosphodiesterase activity

Definition

Target type: molecularfunction

Catalysis of the hydrolysis of 5'-phosphotyrosyl groups formed as covalent intermediates (in DNA backbone breakage) between DNA topoisomerase II and DNA. [PMID:16751265]

5'-tyrosyl-DNA phosphodiesterase activity is a crucial molecular function involved in the repair of DNA damage, specifically focusing on the removal of 3'-tyrosyl residues from DNA. This enzyme plays a vital role in the base excision repair (BER) pathway, a major DNA repair mechanism.

The 3'-tyrosyl residue arises as a byproduct of the action of tyrosyl-DNA phosphodiesterase 1 (Tdp1), which removes 3'-phosphotyrosine from DNA. However, Tdp1's activity can also result in the formation of 3'-tyrosyl residues. To rectify this, 5'-tyrosyl-DNA phosphodiesterase comes into play.

This enzyme specifically cleaves the phosphodiester bond between the 3'-deoxyribose of the DNA backbone and the tyrosine residue, releasing the tyrosyl moiety and restoring the integrity of the DNA strand. This action is critical for ensuring the proper function of the BER pathway and the maintenance of genomic stability.

In essence, 5'-tyrosyl-DNA phosphodiesterase activity is essential for preventing the accumulation of DNA damage, which can lead to mutations, genomic instability, and various diseases, including cancer. This activity is a critical component of the cellular defense mechanism against DNA damage.
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Proteins (1)

ProteinDefinitionTaxonomy
Tyrosyl-DNA phosphodiesterase 2A tyrosyl-DNA phosphodiesterase 2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:O95551]Homo sapiens (human)

Compounds (10)

CompoundDefinitionClassesRoles
beta-lapachonebeta-lapachone : A benzochromenone that is 3,4-dihydro-2H-benzo[h]chromene-5,6-dione substituted by geminal methyl groups at position 2. Isolated from Tabebuia avellanedae, it exhibits antineoplastic and anti-inflammatory activities.

beta-lapachone: antineoplastic inhibitor of reverse transcriptase, DNA topoisomerase, and DNA polymerase
benzochromenone;
orthoquinones
anti-inflammatory agent;
antineoplastic agent;
plant metabolite
camptothecinNSC 100880: carboxylate (opened lactone) form of camptothecin; RN refers to (S)-isomer; structure given in first sourcedelta-lactone;
pyranoindolizinoquinoline;
quinoline alkaloid;
tertiary alcohol
antineoplastic agent;
EC 5.99.1.2 (DNA topoisomerase) inhibitor;
genotoxin;
plant metabolite
n,n'-dibenzoylcystineN,N'-dibenzoylcystine: a low molecular weight gelator; structure in first source
nsc 953971,4-naphthoquinones
1,3(2h,4h)-isoquinolinedione1,3(2H,4H)-isoquinolinedione: structure in first source
nsc 706744
1,3,6-trimethylpyrimido[5,4-e][1,2,4]triazine-5,7-dionepyrimidotriazine
N-(7-phenyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)benzamidepyrimidines
1,6-dimethyl-3-propylpyrimido[5,4-e][1,2,4]triazine-5,7-dionepyrimidotriazine
2,3,4,10-tetrahydro-7,10-dimethyl-2,4-dioxobenzo(g)pteridineflavin