Ape1 abasic dna apurinic or apyrimidinic site lyase. Medical search. Frequent questions

The APEX gene (alternatively named APE1, HAP1, APEN) encodes the major AP endonuclease in human cells. (wikipedia.org)
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)
The data presented support a model by which XRCC1 will pass on the DNA intermediate from hOGG1 to the endonuclease APE1. (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)

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)
Apurinic/apyrimidinic (AP) sites are abundant DNA lesions arising from spontaneous hydrolysis of the N-glycosidic bond and as base excision repair (BER) intermediates. (bvsalud.org)

Here, we report two in vitro models of APPXLs synthesized by cross-linking of DNA glycosylases Fpg and OGG1 to DNA followed by trypsinolysis. (bvsalud.org)

DNA-(apurinic or apyrimidinic site) lyase is an enzyme that in humans is encoded by the APEX1 gene. (wikipedia.org)
DNA Polymerase ß (Polß) is a key enzyme in base excision repair (BER), which is very important in maintaining the stability and integrity of the genome. (bvsalud.org)

Deficiency of APEX1 causes accummulation of DNA damage leading to both cellular senescence and features of premature aging. (wikipedia.org)

In these aggressive resistant ALL cells, POLB depletion and its inhibitor oleanolic acid (OA) treatment result in synthetic lethality with MMR deficiency through increased cellular apurinic/apyrimidinic (AP) sites, DNA strand breaks and apoptosis. (bvsalud.org)

AP sites are pre-mutagenic lesions that can prevent normal DNA replication. (wikipedia.org)

Further results showed that Polß deficiency caused more DNA damage accumulation in cells and triggered the leakage of damaged DNA into the cytoplasm, which activated the STING/IRF3 pathway, promoted phosphorylated IRF3 translocating into the nucleus and enhanced the expression of type I interferon and proinflammatory cytokines. (bvsalud.org)

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)
Here, we provide evidence that DNA polymerase ß (POLB) of base excision repair (BER) pathway plays a critical role in the survival and thiopurine resistance of MMR-deficient ALL cells. (bvsalud.org)

XRCC1 participates in DNA single strand break and base excision repair (BER) to preserve genetic stability in mammalian cells. (nih.gov)
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)

AP sites and their derivatives readily trap DNA-bound proteins, resulting in DNA-protein cross-links. (bvsalud.org)
Our data suggest that APPXLs produced by proteolysis of AP site-trapped proteins may be removed by the BER pathway, at least in bacterial and yeast cells. (bvsalud.org)

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)

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

In contrast, E. coli exonuclease III and human APE1 showed little activity on APPXL substrates. (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 findings provide mechanistic insight into the role of Polß in cancers by linking DNA repair and the inflammatory STING pathway. (bvsalud.org)

However, the repair mechanism of thiopurine-induced DNA damage in the absence of MMR remains unclear. (bvsalud.org)
Our findings suggest BER and POLB's roles in the process of repairing thiopurine-induced DNA damage in MMR-deficient ALL cells, and implicate their potentials as therapeutic targets against aggressive ALL progression. (bvsalud.org)

All cells, from simple prokaryotes to humans, have evolved systems to identify and repair such sites. (wikipedia.org)
Emerging evidence suggests that aberrant DNA repair is an underlying mechanism of lupus development. (bvsalud.org)

This interaction leads to a 2- to 3-fold stimulation of the DNA glycosylase activity of hOGG1. (nih.gov)

Direct metal binding analysis of wild-type, D70A, and E96A APE1, as assessed by differential scanning fluorimetry, indicated a role for D70 and E96 in binding of Mg²⁺ or Mn²⁺ to APE1. (rcsb.org)

A third conformation for E96 in the apo structure is similar to that observed in the APE1-DNA-Mg²⁺ complex structure. (rcsb.org)

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

The APEX gene (alternatively named APE1, HAP1, APEN) encodes the major AP endonuclease in human cells. (wikipedia.org)
The structure of the major human apurinic/ apyrimidinic endonuclease (HAP1) has been solved at 2.2 A resolution. (nih.gov)
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)

UV-DDB, a key protein in human global nucleotide excision repair (NER), binds avidly to abasic sites and 8-oxo-guanine (8-oxoG), suggesting a noncanonical role in base excision repair (BER). (nih.gov)
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)
During short-patch BER, 5′dRP is displaced by DNA polymerase β (Polβ), which inserts a single nucleotide. (springer.com)
The oxidized abasic lesion is also a substrate for the bacterial UvrABC nucleotide excision repair system. (tamu.edu)

We find that human AP endonuclease 1 (APE1) physically interacts with flap endonuclease 1 (FEN1) and with proliferating cell nuclear antigen. (ox.ac.uk)

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)
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)
Excision of a lyase-resistant oxidized abasic lesion from DNA. (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)
We demonstrate that addition of APE1 to the excision reaction mixture slightly (1.5-2-fold) stimulates the removal of the displaced flap by FEN1. (ox.ac.uk)

UV-DDB increased both OGG1 and APE1 strand cleavage and stimulated subsequent DNA polymerase β-gap filling activity by 30-fold. (nih.gov)
These loop regions apparently act in DNA abasic site (AP) recognition and cleavage since DNase I, which lacks these loops, correspondingly lacks AP site specificity. (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)

Furthermore, UV-DDB moves to sites of 8-oxoG repair in cells, and UV-DDB depletion sensitizes cells to oxidative DNA damage. (nih.gov)
The C2'-oxidized abasic lesion (C2-AP) is produced in DNA that is subjected to oxidative stress. (tamu.edu)

Lucanthone inhibits the endonuclease activity of APE1, without affecting its redox activity. (nih.gov)

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)

We propose that UV-DDB is a general sensor of DNA damage in both NER and BER pathways, facilitating damage recognition in the context of chromatin. (nih.gov)

The AP endonucleases cleave an AP site to yield a 3′ hydroxyl adjacent to a 5′ deoxyribosephosphate (dRP). (springer.com)

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)

Lucanthone and hycanthone are thioxanthenone DNA intercalators used in the 1980s as antitumor agents. (nih.gov)

Single-molecule real-time imaging revealed that UV-DDB forms transient complexes with OGG1 or APE1, facilitating their dissociation from DNA. (nih.gov)

The K(D) values (affinity constants) for APE1, as determined by BIACORE binding studies, were 89 nM for lucanthone/10 nM for hycanthone. (nih.gov)
APE1 structures reveal a hydrophobic pocket where hydrophobic small molecules like thioxanthenones can bind, and our modeling studies confirmed such docking. (nih.gov)
This report reviews results from studies, assaying a DNA repair system in HCMV infection. (springer.com)

DNA damages can lead to cell mutation, death, apoptosis and immune system activation. (springer.com)

Organisms8

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HAP13

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