APE1: A skilled nucleic acid surgeon

DNA Repair
Amy M Whitaker, Bret D Freudenthal

Abstract

Before a deleterious DNA lesion can be replaced with its undamaged counterpart, the lesion must first be removed from the genome. This process of removing and replacing DNA lesions is accomplished by the careful coordination of several protein factors during DNA repair. One such factor is the multifunctional enzyme human apurinic/apyrimidinic endonuclease 1 (APE1), known best for its DNA backbone cleavage activity at AP sites during base excision repair (BER). APE1 preforms AP site incision with surgical precision and skill, by sculpting the DNA to place the cleavage site in an optimal position for nucleophilic attack within its compact protein active site. APE1, however, has demonstrated broad surgical expertise, and applies its DNA cleavage activity to a wide variety of DNA and RNA substrates. Here, we discuss what is known and unknown about APE1 cleavage mechanisms, focusing on structural and mechanistic considerations. Importantly, disruptions in the biological functions associated with APE1 are linked to numerous human maladies, including cancer and neurodegenerative diseases. The continued elucidation of APE1 mechanisms is required for rational drug design towards novel and strategic ways to target its associated repair p...Continue Reading

Citations

Dec 13, 2019·Nucleic Acids Research·Yunfeng LinShan Yan
Aug 12, 2020·International Journal of Radiation Biology·Elena A KuznetsovaSvetlana I Zaichkina
Jun 17, 2020·Nucleic Acids Research·Nicole M HoitsmaBret D Freudenthal
Sep 25, 2020·Biomedicines·Yu Ran LeeByeong Hwa Jeon
Sep 22, 2020·Journal of Dermatological Science·Xuyi DengMeijuan Zhou
Oct 30, 2020·OncoTargets and Therapy·Ming-Dian LuYong-Xiang Li
Jan 29, 2021·Nature Communications·Tung-Chang LiuYu-Yuan Hsiao
Feb 1, 2020·Pharmacology & Therapeutics·Erik LauriniSabrina Pricl
Mar 17, 2020·Chemical Research in Toxicology·Haoqing ChenRobert J Turesky
May 27, 2020·DNA Repair·Amy M WhitakerBret D Freudenthal
Mar 7, 2021·International Journal of Molecular Sciences·Scarlett Acklin, Fen Xia
May 10, 2021·Redox Biology·Nadine Müller, Andriy Khobta
Jul 3, 2021·International Journal of Molecular Sciences·David J LópezSonia Bañuelos
Jul 1, 2021·Computational and Structural Biotechnology Journal·Nicole M HoitsmaBret D Freudenthal
Jul 3, 2021·Biology·Marlo K ThompsonAishwarya Prakash
Jul 10, 2021·Signal Transduction and Targeted Therapy·Ruixue Huang, Ping-Kun Zhou
Jul 24, 2021·Journal of Proteomics·Rubén López-CortésCristina Núñez
Aug 21, 2021·DNA Repair·Hossein Ghaderi-ZefrehiMohammad Heiat
Sep 14, 2021·Journal of the American Chemical Society·Kurt HoushKent S Gates

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Methods Mentioned

BETA
X-ray
glycosylases
immunoprecipitation

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