Page last updated: 2024-10-24

NAD DNA ADP-ribosyltransferase activity

Definition

Target type: molecularfunction

Catalysis of the transfer of the ADP-ribose group of NAD+ to a residue in double-stranded DNA. [PMID:27471034, PMID:29361132, PMID:29520010]

NAD DNA ADP-ribosyltransferase activity is a crucial enzymatic function that modifies DNA by attaching ADP-ribose units from NAD+ to specific DNA targets. This process, known as ADP-ribosylation, plays a vital role in various cellular processes, including DNA repair, replication, transcription, and immune responses.

The enzyme responsible for this activity, known as PARP (Poly(ADP-ribose) polymerase), utilizes NAD+ as a substrate to catalyze the transfer of ADP-ribose moieties to DNA. This reaction occurs at specific sites on DNA, primarily at single-strand breaks or other DNA lesions.

Upon DNA damage, PARP enzymes are recruited to the site of damage and initiate the ADP-ribosylation process. They attach ADP-ribose units to DNA, forming a branched, negatively charged polymer called poly(ADP-ribose) (PAR). The formation of PAR chains serves several key functions in DNA repair:

1. **Recruitment of DNA repair proteins:** PAR acts as a signaling molecule, attracting other proteins involved in DNA repair to the site of damage. These proteins include DNA ligases, nucleases, and other repair enzymes.

2. **Chromatin remodeling:** PAR can alter the structure of chromatin, the complex of DNA and proteins that makes up chromosomes. This remodeling facilitates access of repair proteins to damaged DNA.

3. **Regulation of DNA repair pathways:** PAR can influence the activity of specific DNA repair pathways, ensuring efficient and accurate repair of DNA damage.

4. **Signaling for apoptosis:** In cases of severe DNA damage that cannot be repaired, PARP-mediated ADP-ribosylation can trigger apoptotic pathways, leading to cell death.

Overall, NAD DNA ADP-ribosyltransferase activity is a fundamental process involved in maintaining genomic integrity and cellular function. By regulating DNA repair, chromatin structure, and signaling pathways, this activity plays a crucial role in protecting cells from the deleterious effects of DNA damage.'
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Proteins (3)

ProteinDefinitionTaxonomy
Protein mono-ADP-ribosyltransferase PARP3A protein mono-ADP-ribosyltransferase PARP3 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9Y6F1]Homo sapiens (human)
Poly [ADP-ribose] polymerase 2A poly [ADP-ribose] polymerase 2 that is encoded in the genome of human. [PRO:DNx]Homo sapiens (human)
Poly [ADP-ribose] polymerase 1A poly [ADP-ribose] polymerase 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P09874]Homo sapiens (human)

Compounds (55)

CompoundDefinitionClassesRoles
niacinamidenicotinamide : A pyridinecarboxamide that is pyridine in which the hydrogen at position 3 is replaced by a carboxamide group.pyridine alkaloid;
pyridinecarboxamide;
vitamin B3
anti-inflammatory agent;
antioxidant;
cofactor;
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor;
EC 3.5.1.98 (histone deacetylase) inhibitor;
Escherichia coli metabolite;
geroprotector;
human urinary metabolite;
metabolite;
mouse metabolite;
neuroprotective agent;
Saccharomyces cerevisiae metabolite;
Sir2 inhibitor
1,5-dihydroxyisoquinoline1,5-dihydroxyisoquinoline: structure in first source

isoquinoline-1,5-diol : An isoquinolinol that is isoquinoline in which the hydrogens at positions 1 and 5 are replaced by hydroxy groups.
isoquinolinolEC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor
3-aminobenzamidebenzamides;
substituted aniline
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor
4-amino-1,8-naphthalimide4-amino-1,8-naphthalimide: inhibits ADP-ribosylation; sometimes abreviated as 4-AN;benzoisoquinoline;
dicarboximide
phenanthridonephenanthridone : A member of the class of phenanthridines that is phenanthridine with an oxo substituent at position 6. A poly(ADP-ribose) polymerase (PARP) inhibitor, it has been shown to exhibit immunosuppressive activity.

phenanthridone: coal tar derivative; structure given in first source
lactam;
phenanthridines
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor;
immunosuppressive agent;
mutagen
5-aminoisoquinolinone5-aminoisoquinolinone: structure in first sourceisoquinolines
benzamidebenzamide : An aromatic amide that consists of benzene bearing a single carboxamido substituent. The parent of the class of benzamides.benzamides
pj-34PJ34 : A member of the class of phenanthridines that is 5,6-dihydrophenanthridine substituted at positions 2 and 6 by (N,N-dimethylglycyl)amino and oxo groups, respectively. It is a potent inhibitor of poly(ADP-ribose) polymerases PARP1 and PARP2 (IC50 of 110 nM and 86 nM, respectively) and exhibits anti-cancer, cardioprotective and neuroprotective properties.phenanthridines;
secondary carboxamide;
tertiary amino compound
angiogenesis inhibitor;
anti-inflammatory agent;
antiatherosclerotic agent;
antineoplastic agent;
apoptosis inducer;
cardioprotective agent;
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor;
neuroprotective agent
3-aminobenzoic acid3-aminobenzoic acid : An aminobenzoic acid carrying an amino group at position 3.

3-aminobenzoic acid: RN given refers to parent cpd
aminobenzoic acid
1-hydroxyphthalazine1-hydroxyphthalazine: RN given refers to cpd with unspecified locants; do not confuse with cpd phthalazinol RN: 56611-65-5phthalazines
chlorthenoxazinchlorthenoxazin: RN given refers to parent cpd; structurebenzoxazine
isocarbostyrilisoquinolinone : An isoquinoline containing one or more oxo groups.isoquinolines
flavoneflavone : The simplest member of the class of flavones that consists of 4H-chromen-4-one bearing a phenyl substituent at position 2.

flavone: RN given refers to unlabeled cpd; structure given in first source
flavonesmetabolite;
nematicide
2,4(1h,3h)-quinazolinedione2,4(1H,3H)-quinazolinedione: structure given in first source
4-hydroxybenzamide
naphthalimidesNaphthalimides: Compounds with three fused rings that appear like a naphthalene fused to piperidone or like a benz(de)isoquinoline-1,3-dione (not to be confused with BENZYLISOQUINOLINES which have a methyl separating the naphthyl from the benzyl rings). Members are CYTOTOXINS.
4-fluorobenzamide4-fluorobenzamide: structure in first source
5-iodo-6-amino-1,2-benzopyrone
alantolactonealantolactone : A sesquiterpene lactone that is 3a,5,6,7,8,8a,9,9a-octahydronaphtho[2,3-b]furan-2-one bearing two methyl substituents at positions 5 and 8a as well as a methylidene substituent at position 3.

alantolactone: allergenic sesquiterpene lactone; crystalline mixture of alantolactones from group of sesquiterpenes; structure
naphthofuran;
olefinic compound;
sesquiterpene lactone
antineoplastic agent;
apoptosis inducer;
plant metabolite
4-aminobenzamidebenzamides
4-Methoxybenzamidebenzamides
3-methoxybenzamide
3',4'-dihydroxyflavone3',4'-dihydroxyflavone: inhibitors of arachidonic acid peroxidation
3,4-dihydro-5-methyl-1(2h)-isoquinolinone3,4-dihydro-5-methyl-1(2H)-isoquinolinone: structure given in first sourceisoquinolines
1-oxo-1,2,3,4-tetrahydroisoquinoline1-oxo-1,2,3,4-tetrahydroisoquinoline: structure given in first source
cyclo(alanylalanyl)
N-[4-[[[4-(4-methoxyphenyl)-4-oxanyl]methylamino]-oxomethyl]phenyl]-2-furancarboxamidearomatic amide;
furans
ha 1100HA 1100: intracellular calcium antagonist
apigeninChamomile: Common name for several daisy-like plants (MATRICARIA; TRIPLEUROSPERMUM; ANTHEMIS; CHAMAEMELUM) native to Europe and Western Asia, now naturalized in the United States and Australia.trihydroxyflavoneantineoplastic agent;
metabolite
luteolin3'-hydroxyflavonoid;
tetrahydroxyflavone
angiogenesis inhibitor;
anti-inflammatory agent;
antineoplastic agent;
apoptosis inducer;
c-Jun N-terminal kinase inhibitor;
EC 2.3.1.85 (fatty acid synthase) inhibitor;
immunomodulator;
nephroprotective agent;
plant metabolite;
radical scavenger;
vascular endothelial growth factor receptor antagonist
amentoflavonebiflavonoid;
hydroxyflavone;
ring assembly
angiogenesis inhibitor;
antiviral agent;
cathepsin B inhibitor;
P450 inhibitor;
plant metabolite
3',4',7-trihydroxyflavone3',4',7-trihydroxyflavone: from the Sudanese medicinal plant Albizia zygia; structure in first sourceflavones
adenosine diphosphate (hydroxymethyl)pyrrolidinedioldihydroxypyrrolidine;
purine ribonucleoside 5'-diphosphate
ag 14361benzimidazoles
gpi 6150
rucaparibAG14447: Poly(ADP-ribose) polymerase inhibitor; structure in first sourceazepinoindole;
caprolactams;
organofluorine compound;
secondary amino compound
antineoplastic agent;
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor
3,4-dihydro-5-(4-(1-piperidinyl)butoxy)-1(2h)-isoquinolinone
latonduine alatonduine A: structure in first source
veliparibbenzimidazolesEC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor
olaparibcyclopropanes;
monofluorobenzenes;
N-acylpiperazine;
phthalazines
antineoplastic agent;
apoptosis inducer;
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor
niraparib2-[4-(piperidin-3-yl)phenyl]-2H-indazole-7-carboxamide : A member of the class of indazoles that is 2H-indazole substituted by 4-(piperidin-3-yl)phenyl and aminocarbonyl groups at positions 2 and 7, respectively. It is a potent PARP1 inhibitor with IC50 of 3.2 nM.benzenes;
indazoles;
piperidines;
primary carboxamide
antineoplastic agent;
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor
niraparibniraparib : A 2-[4-(piperidin-3-yl)phenyl]-2H-indazole-7-carboxamide that has S-configuration. It is a potent inhibitor of PARP1 and PARP2 (IC50 of 3.8 and 2.1 nM, respectively) and approved as a first-line maintenance treatment for women with advanced ovarian cancer after responding to platinum-based chemotherapy.

niraparib: structure in first source
2-[4-(piperidin-3-yl)phenyl]-2H-indazole-7-carboxamideantineoplastic agent;
apoptosis inducer;
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor;
radiosensitizing agent
cep 26401pyridazines;
ring assembly
iwr-1 endoIWR-1-endo : A dicarboximide having an endo bridged phthalimide structure, substituted at nitrogen by a 4-(quinolin-8-ylcarbamoyl)benzoyl group.benzamides;
bridged compound;
dicarboximide;
quinolines
axin stabilizer;
Wnt signalling inhibitor
nms-p118NMS-P118: a PARP-1 inhibitor; structure in first source
g007-lkG007-LK: potent and specific small-molecule tankyrase inhibitor; structure in first source
nu 1025NU 1064: structure in first sourcephenols;
quinazolines
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor
2-methyl-4(3h)-quinazolinone2-methyl-4(3H)-quinazolinone: from Bacillus cereus; structure given in first source
4-hydroxyquinazoline4-oxo-3,4-dihydroquinazoline: structure in first sourcequinazolines
1,4-Dihydrothieno[3,2-d]pyrimidin-4-oneorganic heterobicyclic compound;
organonitrogen heterocyclic compound;
organosulfur heterocyclic compound
xav939XAV939 : A thiopyranopyrimidine in which a 7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine skeleton is substituted at C-4 by a hydroxy group and at C-2 by a para-(trifluoromethyl)phenyl group.

XAV939: selectively inhibits beta-catenin-mediated transcription; structure in first source
(trifluoromethyl)benzenes;
thiopyranopyrimidine
tankyrase inhibitor
2-(4-methoxyphenyl)-1H-quinazolin-4-onequinazolines
bmn 673talazoparib: inhibits both PARP1 and PARP2; structure in first source
me0328ME0328: inhibits ARTD3; structure in first source
nvp-tnks656