Catalytic properties of human apurinic/apyrimidinic endonuclease 1 (APE1) and development of biosensors of APE1 in living cells

• Main Author: Wang, Tianxiang
• Other Authors: Li Tianhu
• Format: Thesis-Doctor of Philosophy
• Language: English
• Published: Nanyang Technological University 2021
• Subjects: Science::Chemistry::Biochemistry
• Online Access: https://hdl.handle.net/10356/147410
• Institution: Nanyang Technological University

Apurinic/apyrimidinic endonuclease 1 (APE1) is an essential enzyme involved in the DNA base excision repair pathway and responsible for restoring mutagenic and cytotoxic abasic lesions throughout cell cycles. APE1 will cleave the 5’ end phosphodiester backbone right next to the generated apurinic/apyrimidinic site (AP site) to produce a free 5’ phosphate termini linking to the AP site and a free 3’ hydroxyl termini on the regular nucleotide. APE1 is overexpressed in various types of cancer cells, proving that APE1 is a valid biomarker for cancer diagnosis and its inhibitors show potential in monotherapy and combination therapy for fighting cancers. In spite of its potential roles in cancer diagnosis, prognosis, and chemotherapy, however, various aspects of translational research about APE1 have not yet been carried out thus far. Herein, we have successfully developed graphene quantum dot-based biosensors for APE1 diagnosis both in cell-free systems and in living cells. Besides, investigation on diversity of substrates makes a great contribution to understand the catalytic properties of APE1 and further explore sequence-specific DNA as new APE1 inhibitors.