Abasic bases from dna dna apurinic or apyrimidinic site lyase. Medical search. Frequent questions

Class II AP endonucleases cleave the phosphodiester backbone 5' to the AP site, thereby initiating a process known as base excision repair (BER). (wikipedia.org)
XRCC1 participates in DNA single strand break and base excision repair (BER) to preserve genetic stability in mammalian cells. (nih.gov)
Apurinic/apyrimidinic endonuclease I (APE1) is an essential base excision repair enzyme that catalyzes a Mg²⁺-dependent reaction in which the phosphodiester backbone is cleaved 5' of an abasic site in duplex DNA. (rcsb.org)
In human cells, the enzymatic activities initiating DNA base excision repair (BER) of 8-oxoG, U and AP sites are the 8-oxoG DNA glycosylase (hOGG1), the U-DNA glycosylase (UNG) and the major hydrolytic AP endonuclease (APE/HAP1), respectively. (utmb.edu)
Base excision repair (BER) is a highly conserved DNA repair pathway throughout all kingdoms from bacteria to humans. (ox.ac.uk)

Whereas several enzymes are required to complete the multistep repair process of damaged bases, apurinic-apyrimidic (AP) endonucleases play an essential role in enabling the repair process by recognizing intermediary abasic sites cleaving the phosphodiester backbone 5' to the abasic site. (ox.ac.uk)

Apurinic/apyrimidinic (AP) sites (also called "abasic sites") occur frequently in DNA molecules by spontaneous hydrolysis, by DNA damaging agents or by DNA glycosylases that remove specific abnormal bases. (wikipedia.org)

DNA-(apurinic or apyrimidinic site) lyase is an enzyme that in humans is encoded by the APEX1 gene. (wikipedia.org)
Deficiency of APEX1 causes accummulation of DNA damage leading to both cellular senescence and features of premature aging. (wikipedia.org)

All cells, from simple prokaryotes to humans, have evolved systems to identify and repair such sites. (wikipedia.org)

Structural basis for the recognition and cleavage of abasic DNA in Neisseria meningitidis. (ox.ac.uk)
Our data reveal subtle differences in AP-site recognition and kinetics between the human and bacterial enzymes that may reflect different evolutionary pressures. (ox.ac.uk)

More importantly, the results unveil a highly coordinated mechanism by which XRCC1, through its multiple protein-protein interactions, extends its orchestrating role from the base excision step to the resealing of the repaired DNA strand. (nih.gov)

This results in an acceleration of the overall repair process of oxidized purines to yield an APE1-cleaved abasic site, which can be used as a substrate by DNA polymerase beta. (nih.gov)
Despite extensive study, there is no structure of a bacterial AP endonuclease bound to substrate DNA. (ox.ac.uk)

XRCC1 stimulates the formation of the hOGG1 Schiff-base DNA intermediate without interfering with the endonuclease activity of APE1, the second enzyme in the pathway. (nih.gov)
Addition to reaction mixtures of titrated amounts of purified hOGG1, UNG and APE/HAP1 variably stimulated the in vitro repair replication of 8-oxoG, U and the AP site respectively and the increase was not always proportional to the amount of added enzyme. (utmb.edu)

DNA polymerase (pol) Î· is responsible for error-free translesion DNA synthesis (TLS) opposite ultraviolet light (UV)-induced cis-syn cyclobutane thymine dimers (CTDs) and cisplatin-induced intrastrand guanine crosslinks. (bvsalud.org)

Here, we report that XRCC1 interacts physically and functionally with hOGG1, the human DNA glycosylase that initiates the repair by BER of the mutagenic oxidized base 8-oxoguanine. (nih.gov)
This interaction leads to a 2- to 3-fold stimulation of the DNA glycosylase activity of hOGG1. (nih.gov)
The data presented support a model by which XRCC1 will pass on the DNA intermediate from hOGG1 to the endonuclease APE1. (nih.gov)

Ribosomal protein S3 (RpS3) is involved in protein biosynthesis as a component of the ribosome complex and possesses endonuclease activity to repair damaged DNA. (bmbreports.org)

AP sites are pre-mutagenic lesions that can prevent normal DNA replication. (wikipedia.org)
The oxidized base 8-oxo-7,8-dihydroguanine (8-oxoG), the product of deamination of cytosine uracil (U), and the sites of base loss [abasic (AP) sites] are among the most frequent mutagenic lesions formed in the human genome under physiological conditions. (utmb.edu)

Furthermore, the structural mechanism for AP-site cleavage is incomplete. (ox.ac.uk)

Lyn, a tyrosine kinase that is activated by double-stranded DNA-damaging agents, is involved in various signaling pathways, such as proliferation, apoptosis, and DNA repair. (bmbreports.org)

A third conformation for E96 in the apo structure is similar to that observed in the APE1-DNA-Mg²⁺ complex structure. (rcsb.org)
Thus, binding of Mg²⁺ in three different positions within the active site of APE1 in these crystal structures corresponds directly with three different conformations of E96. (rcsb.org)

We evaluated the functional properties of eight human POLH germline in silico-predicted deleterious missense variants, using biochemical and cell-based assays. (bvsalud.org)

This finding is consistent with the theory that DNA damage is a primary cause of aging. (wikipedia.org)

The increase in ethylene emission resulted in enhanced hydrogen peroxide concentration, phenylalanine ammonia-lyase activity, ß-1,3 glucanase activity, and expression profiles of WRKY, CaPR1, and CaPTI1 genes that are typical salt stress and PR signaling factors. (bvsalud.org)

This reaction has been proposed to involve either one or two metal ions bound to the active site. (rcsb.org)

Taken together, our results are consistent with the initial capture of metal by D70 and E96 and repositioning of Mg²⁺ facilitated by the structural plasticity of E96 in the active site. (rcsb.org)

An example of an endonuclease that will act on an AP sites is Endo IV. (neb.com)
To cleave the DNA backbone, another enzyme such as Endonuclease VIII is required. (neb.com)
However, apyrimidinic/apurinic (AP) endonuclease-deficient cells (xth nfo strain) were very sensitive to killing by NO(.), which indicates that normal processing of abasic sites is critical for defense against NO(.). In addition, recA mutant cells were exquisitely sensitive to NO(.)-induced killing. (nih.gov)
APEX1 is the major endonuclease in human cells, playing a role in DNA repair and the celluar response to oxidative stress. (nih.gov)
The iron-sulphur cluster loop (FCL) is also found in DNA-(apurinic or apyrimidinic site) lyase, a subfamily of endonuclease III. (embl-heidelberg.de)
The enzyme has both apurinic and apyrimidinic endonuclease activity and a DNA N-glycosylase activity. (embl-heidelberg.de)
The structure of the major human apurinic/ apyrimidinic endonuclease (HAP1) has been solved at 2.2 A resolution. (nih.gov)
Structural comparison of AP endonucleases from the exonuclease III family reveals new amino acid residues in human AP endonuclease 1 that are involved in incision of damaged DNA. (nih.gov)
Human HAP1 (REF1) encodes the major AP endonuclease which, in addition to its role in DNA repair, functions as a redox regulatory protein. (houstonmethodist.org)
Endonuclease V (EndoV) in E. coli is active upon DNA exposed to UV light, OsO4, acids, or X-rays [ 10 ]. (biomedcentral.com)
This enzyme was later characterized as 3′-deoxyinosine endonuclease that incises the DNA at the second phosphodiester bond 3′ to the dI lesion, leaving 3′-OH and 5′-P termini [ 13 ]. (biomedcentral.com)

Class II AP endonucleases cleave the phosphodiester backbone 5' to the AP site, thereby initiating a process known as base excision repair (BER). (wikipedia.org)
Excision of a lyase-resistant oxidized abasic lesion from DNA. (tamu.edu)
The oxidized abasic lesion is also a substrate for the bacterial UvrABC nucleotide excision repair system. (tamu.edu)
These data suggest that the redundant nature of DNA repair systems provides a means for removing a lesion that resists excision by short patch base excision repair. (tamu.edu)
Various types of DNA damage are repaired through multiple repair pathways, such as base excision, nucleotide excision, homologous recombination and nonhomologous end joining. (springer.com)
There are six known systems of DNA repair: pathway of direct reversion of damage, base excision repair (BER), nucleotide-excision repair (NER), mismatch repair (MMR), homologous recombination (HR) and nonhomologous DNA end joining (NHEJ). (springer.com)
The base excision repair (BER) pathway corrects most endogenous base lesions, including alkylation, oxidation and deamination, apurinic/apyrimidinic (AP) sites as well as single-strand breaks. (springer.com)
The base excision repair (BER) system. (springer.com)
The relative importance of base excision repair, nucleotide excision repair (NER), and recombinational repair in preventing NO(.)-induced toxicity was determined. (nih.gov)
APEX1 is an apurinic/apyrimidinic (AP) endodeoxyribonuclease in the DNA base excision repair (BER) pathway of DNA lesions induced by oxidative and alkylating agents. (nih.gov)
Escherichia coli MutY is an adenine glycosylase involved in base excision repair that recognizes OG:A (where OG = 7, 8-dihydro-8-oxo-2'-deoxyguanosine) and G:A mismatches in DNA. (embl-heidelberg.de)
This activity coordinates with the polymerization and ligase activities to allow efficient repairing of an AP site-containing DNA in an in vitro reconstituted Base Excision Repair (BER) reaction. (uam.es)
An oligonucleotide substrate containing a reduced abasic site, which was pre-incised with APE1, was employed to reconstitute the excision step of long-patch BER with purified human DNA polymerase beta and FEN1. (ox.ac.uk)
In mammalian cells, base excision repair (BER) was thought to be the major pathway for dI repair. (biomedcentral.com)
The excision of base damage is initiated by a specific DNA glycosylase: Hypoxanthine is bound and excised efficiently by human N -methylpurine-DNA glycosylase (MPG, also known as AAG, ANPG, APNG, or MDG) [ 6 ]. (biomedcentral.com)

The HAP1 structure furthermore suggests a mechanism for AP site binding which involves the recognition of the deoxyribose moiety in an extrahelical conformation, rather than a 'flipped-out' base opposite the AP site. (nih.gov)
We identify APN2, the yeast homolog of HAP1 and provide evidence that Apn1 and Apn2 represent alternate pathways for repairing AP sites. (houstonmethodist.org)

Ape1 incises C2-AP, but the 5'-phosphorylated fragment is not a substrate for the lyase activity of DNA polymerase beta. (tamu.edu)

A damaged base is recognized by a specific DNA glycosylase, which cleaves the bond between the base and sugar, creating an abasic site (AP), which is a mutagenic and cytotoxic intermediate. (springer.com)
The AP lyase activity of Fpg cleaves an AP site, via beta and delta-elimination, creating a 1 nucleotide DNA gap with 5-prime and 3-prime phosphate termini. (neb.com)
Thermostable FEN1, for example, recognizes a specific FLAP structure, and cleaves this flap leaving a 5-prime phosphate, which can then be ligated with a DNA ligase. (neb.com)

Nfi homologues from Thermotoga maritima possess 3′-exonuclease activity that might be used for removal of damaged bases [ 14 ], but similar exonuclease activities were not found in EndoV from E. coli and mammalian cells. (biomedcentral.com)

Fpg is a bifunctional DNA glycosylase with DNA N-glycosylase and AP lyase activities. (neb.com)
N-glycosylase activity releases damaged purines, including 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG) and 8-oxo-7,8-dihydroguanine (8-oxoG), generating an AP site. (neb.com)
In Escherichia coli , early studies indicated that the DNA glycosylase encoded by alkA gene could recognize and release hypoxanthine residues from DNA [ 1 ]. (biomedcentral.com)

The C2'-oxidized abasic lesion (C2-AP) is produced in DNA that is subjected to oxidative stress. (tamu.edu)

Deoxyinosine (hypoxanthine deoxyribonucleotide, dI) in DNA can arise from spontaneous deamination of deoxyadenosine residue, and is also induced by ROS produced from normal aerobic respiration. (biomedcentral.com)
Deoxyinosine derived from deamination of deoxyadenosine in DNA is potentially mutagenic since it prefers to pair with dCTP during replication, yielding A:T to G:C transition mutations at sites of adenine deamination [ 5 ]. (biomedcentral.com)

Structure-dependent endos, which include wide variety of DNA repair enzymes, require a specific DNA structure or damaged base for activity, and will cleave an internal phosphodiester bond at that structure or damaged base. (neb.com)
After its recruitment by Ku, LigD would form a complex with the DNA, most probably implying the interaction of Lys331 with one of the phosphates of the phosphodiester bond between the AP site and the next 3' nucleotide ( b ). (uam.es)

It catalyzes the cleavage of DNA phosphodiester backbone at AP sites via hydrolysis, leaving a 1 nucleotide gap with 3´-hydroxyl and 5´-deoxyribose phosphate (dRP) termini. (neb.com)
Coupling of AP sites cleavage to the end-joining reaction by the B. subtilis LigD. (uam.es)

All cells, from simple prokaryotes to humans, have evolved systems to identify and repair such sites. (wikipedia.org)
The control aspects of the five DNA repair mechanisms in virus-infected cells have not been well characterized. (springer.com)
Our main objective is to get insights on the molecular mechanisms responsible for maintaining genome stability in bacteria, by functional analysis of the enzymatic features of purified repair proteins from model organisms as the gram positive bacterium Bacillus subtilis whose vegetative cells and spores have to handle DNA damage induced by extreme environmental conditions, and the gram negative Pseudomonas aeruginosa . (uam.es)
A plasmid-based convenient and non-radioisotopic method was created to study dI repair in human cells. (biomedcentral.com)

Maintenance of genome stability largely relies on faithful DNA replication. (uam.es)
Hypoxanthine in DNA can pair with cytosine which results in A:T to G:C transition mutations after DNA replication. (biomedcentral.com)

Therefore, LigD has in the same polypeptidic chain the three activities required in the last steps of BER, suggesting that its DNA repair role is not restricted to the NHEJ pathway, but expands beyond, being potentially active in additional repair pathways. (uam.es)
From radionucleotide incorporation fine mapping, the resulting apurinic/apyrimidinic (AP) sites are further processed by both the short patch pathway (1-nucleotide gap filling) with DNA polymerase (Pol) β and the long patch pathway (2-6 nucleotide resynthesis) with Pol δ and PCNA [ 7 ]. (biomedcentral.com)

Abasic (AP) sites arise in DNA through spontaneous base loss and enzymatic removal of damaged bases. (houstonmethodist.org)

Our findings indicate that AP sites are highly cytotoxic and mutagenic in eukaryotes, and that the REV3, REV7-encoded DNA polymerase ζ mediates the mutagenic bypass of AP sites. (houstonmethodist.org)

The AP endonucleases cleave an AP site to yield a 3′ hydroxyl adjacent to a 5′ deoxyribosephosphate (dRP). (springer.com)
Endonucleases cleave DNA internally, and do not require free DNA ends for activity. (neb.com)
Structure-independent endos randomly cleave internal phosphodiester bonds, and are named such because they do not require a specific DNA structure for activity. (neb.com)
These are processive enzymes, and once activity has been initiated, the endo will continue to cleave DNA. (neb.com)

Examples of structure-independent endos active on double-stranded DNA are micrococcal nuclease and DNase I. An example of a structure-independent endo active on single-stranded DNA is mung bean nuclease. (neb.com)

Apurinic or apyrimidinic sites, also known AP or abasic sites are common and occur spontaneously in DNA when a base is lost. (neb.com)

Free radical attack on C1' of deoxyribose forms the oxidized abasic (AP) site 2-deoxyribonolactone (dL). (nih.gov)

During short-patch BER, 5′dRP is displaced by DNA polymerase β (Polβ), which inserts a single nucleotide. (springer.com)

In this study, we have explored the biological effects of NO(.)-induced DNA damage on Escherichia coli. (nih.gov)

The properties of the R194A, K196A, and K198A enzymes were also compared to the properties of mutated enzymes in which lysine residues near the active site pocket were replaced with alanine or glycine. (embl-heidelberg.de)

DNA polymerase (pol) Î· is responsible for error-free translesion DNA synthesis (TLS) opposite ultraviolet light (UV)-induced cis-syn cyclobutane thymine dimers (CTDs) and cisplatin-induced intrastrand guanine crosslinks. (bvsalud.org)

The templating nucleotide opposite the AP site directs the binding of the complementary ribonucleotide, forming a Watson-Crick base pair at the polymerization site of the PolDom ( c ). (uam.es)

We also offer solutions for automation, site-directed mutagenesis, as well as your favorite restriction enzyme, ligase or competent cell products. (neb.com)

In vivo , the primary role of endonucleases is to repair damaged DNA. (neb.com)

In this review, considerations and results of the experiments are presented, supporting the thesis on the important role of DNA repair systems in HCMV- infected cell. (springer.com)

However, only the K198A enzyme exhibited a significant reduction (15-fold) of the rate of adenine removal from a G:A base pair-containing duplex. (embl-heidelberg.de)

Once the preternary-precatalytic complex is stabilized, the protein incises at the AP site, releasing the cleaved strand and giving rise to a new 5'-P end ( d ). (uam.es)

USER Enzyme contains a mixture of these two enzymes so that the damage is completely removed, and the AP site is cleaved. (neb.com)
Aside from DNA repair enzymes, there are also structure-specific endonucleases that act on DNA secondary structure. (neb.com)

Structure-independent endos are primarily used to clean-up DNA contamination. (neb.com)
After the breakage, the DNA end is threaded through the open ring-like structure of the Ku dimer ( a ). (uam.es)

Furthermore, these results suggest that the FCL motif is intimately involved in the base removal process. (embl-heidelberg.de)

DNA damage normally triggers activities of the cellular DNA repair machinery. (springer.com)
The viruses that induce cellular DNA damage include members of the herpesvirus group, adenovirus, mumps-virus, measles-virus, rubella-virus, poliovirus and papilloma-virus (Fortunato et al. (springer.com)
Those experimental studies focused on repairs of exogenously introduced damage in cellular DNA in the context of single viral protein expression (Becker et al. (springer.com)

DNA damages can lead to cell mutation, death, apoptosis and immune system activation. (springer.com)
Unrepaired DNA damage can lead to mutation, development of various diseases or cell death (Bartek et al. (springer.com)

Anatomy2

Organisms2

Chemicals and Drugs63

Analytical, Diagnostic and Therapeutic Techniques and Equipment4

Phenomena and Processes23

Information Science3

Health Care1

Excision repair5

Cleaving the phosphodiester1

Glycosylases1

APEX12

Humans1

Recognition2

Protein-protein inte1

Substrate2

Enzyme2

Polymerase1

HOGG13

Endonuclease activity1

Lesions2

Mechanism1

Repair1

APE12

Human1

Damage1

Activity1

Bound1

Structural1

Endonuclease11

Excision15

HAP12

Polymerase Beta1

Cleaves3

Mammalian cells1

Glycosylase3

Oxidative stress1

Deamination2

Phosphodiester bond2

Cleavage2

Cells4

Replication2

Pathway2

Spontaneous1

Mutagenic1

Cleave4

Nuclease1

Occur1

Deoxyribose1

Single nucleotide1

Escherichia1

Residues1

Synthesis1

Opposite1

Ligase1

Vivo1

Role1

Adenine1

Incises1

Enzymes2

Structure2

Removal1

Cellular3

Mutation2