The exonuclease activity of APE2 is strongly dependent upon metal ions. (wikipedia.org)
In addition, we identified a small molecule compound Celastrol as an APE2 inhibitor that specifically compromises the binding of APE2 but not RPA to ssDNA and 3'-5' exonuclease activity of APE2 but not APE1. (nih.gov)
Protein called3
NIEHS and Canadian scientists discover that cancer cells with mutated BRCA1 and BRCA2 genes died when they lacked a protein called APE2. (nih.gov)
The vulnerability arises when a protein called APE2 is also lost. (nih.gov)
The 5-year grant (NIH R01CA225637) Yan's lab has received will support the continuation of the lab's study of the mechanism of a repair protein called APE1 in DNA damage response. (charlotte.edu)
Regulator2
APE2 Is a General Regulator of the ATR-Chk1 DNA Damage Response Pathway to Maintain Genome Integrity in Pancreatic Cancer Cells. (nih.gov)
However, it remains unclear whether APE2 is a general regulator of the DDR pathway in mammalian cells. (nih.gov)
Tumor2
As such, knocking down APE1 could lead to tumor cell sensitivity, thus preventing cancer cells from persisting after chemotherapy. (wikipedia.org)
Removal of another leg - APE2 - causes the system to topple, resulting in death of the tumor cells. (nih.gov)
Chemotherapy2
Because APE1 performs an essential function in DNA base-excision repair pathway, it has become a target for researchers looking for means to prevent cancer cells from surviving chemotherapy. (wikipedia.org)
Notably, cell viability assays demonstrate that APE2-KD or Celastrol sensitizes pancreatic cancer cells to chemotherapy drugs. (nih.gov)
Promotes2
14. Differential expression of APE1 and APE2 in germinal centers promotes error-prone repair and A:T mutations during somatic hypermutation. (nih.gov)
One of the most recent papers, "APE2 promotes DNA damage response pathway from a single-strand break," was published in January 2018 in the journal Nucleic Acids Research (Oxford University Press). (charlotte.edu)
Regulation3
The impairment of ATR-Chk1 DDR pathway by Celastrol in Xenopus egg extracts and human pancreatic cancer cells highlights the physiological significance of Celastrol in the regulation of APE2 functionalities in genome integrity. (nih.gov)
Williams' lab continues to study APE2, working with other NIEHS researchers to further understand the role and regulation of APE2 in processing ribonucleotides embedded in DNA. (nih.gov)
While APE1 is known for its critical functions in base excision repair and transcriptional regulation, it is currently unknown whether APE1 plays an essential role in DNA damage response pathway. (charlotte.edu)
Pathway4
Not only is APE1 needed in and of itself to create the nick in the DNA backbone so that the enzymes involved later in the BER pathway can recognize the AP-site, it also has a redox function that helps activate other enzymes involved in DNA repair. (wikipedia.org)
Recent studies have revealed that APE2 is required to activate an ATR-Chk1 DNA damage response (DDR) pathway in response to oxidative stress and a defined DNA single-strand break (SSB) in Xenopus laevis egg extracts. (nih.gov)
Here, we provide evidence using human pancreatic cancer cells that APE2 is essential for ATR DDR pathway activation in response to different stressful conditions including oxidative stress, DNA replication stress, and DNA double-strand breaks. (nih.gov)
Recent studies have revealed that APE2 is required for the activation of an ATR-Chk1 DNA damage response (DDR) pathway in response. (charlotte.edu)
Repair3
Human AP endonuclease (APE1), like most AP endonucleases, is of class II and requires an Mg2+ in its active site in order to carry out its role in base excision repair. (wikipedia.org)
APE1 is active in a different repair process, called base excision repair. (nih.gov)
This finding suggested that APE2 helps repair damage from natural body processes, or endogenous damage, such as RNA lesions (see sidebar ). (nih.gov)
Human3
APE1 exhibits robust AP-endonuclease activity, which accounts for >95% of the total cellular activity, and APE1 is considered to be the major AP endonuclease in human cells. (wikipedia.org)
In addition, the APE2 protein has a C-terminal extension, which is not present in APE1, but can also be found in homologs of human APE2 such as APN2 proteins of S. cerevisiae and S. pombe. (wikipedia.org)
Role1
Because of Williams lab's expertise in APE2 structure, Dan Durocher, Ph.D. , from the Lunenfeld-Tanenbaum Research Institute in Toronto, contacted him in hope that together they could uncover the role of APE2 in BRCA-deficient tumors. (nih.gov)
Active3
However, APE2 was more than 5-fold more active in the presence of manganese than of magnesium ions. (wikipedia.org)
Meanwhile, an Asp210 in the active site, which is made more reactive due to the increase in its pKa (or the negative log of acid dissociation constant) caused through its stabilization through its hydrogen bonding between Asn68 and Asn212, activates the nucleophile that attacks and cleaves the phosphodiester backbone and probably results in the observed maximal APE1 activity at a pH of 7.5. (wikipedia.org)
Further, both contain many H-bond acceptors which may interact with the H-bond donors in the active site of APE1, causing these inhibitors to stick in the active site and preventing the enzyme from catalyzing other reactions. (wikipedia.org)