AUF1 Recognizes 8-Oxo-Guanosine Embedded in DNA and Stimulates APE1 Endoribonuclease Activity

Overview

Journal Antioxid Redox Signal

Specialty Endocrinology

Date 2023 Mar 1

PMID 36855946

Authors

Matilde Clarissa Malfatti

Marta Codrich

Emiliano Dalla

Chiara DAmbrosio

Francesca Storici

Andrea Scaloni

Gianluca Tell

Affiliations

Soon will be listed here.

Abstract

The existence of modified ribonucleotide monophosphates embedded in genomic DNA, as a consequence of oxidative stress conditions, including 8-oxo-guanosine and ribose monophosphate abasic site (rAP), has been recently highlighted by several works and associated with oxidative stress conditions. Although human apurinic-apyrimidinic endodeoxyribonuclease 1 (APE1), a key enzyme of the base-excision repair pathway, repairs rAP sites and canonical deoxyribose monophosphate abasic sites with similar efficiency, its incision-repairing activity on 8-oxo-guanosine is very weak. The aims of this work were to: (i) identify proteins able to specifically bind 8-oxo-guanosine embedded in DNA and promote APE1 endoribonuclease activity on this lesion, and (ii) characterize the molecular and biological relevance of this interaction using human cancer cell lines. By using an unbiased proteomic approach, we discovered that the AU-rich element RNA-binding protein 1 (AUF1) actively recognizes 8-oxo-guanosine and stimulates the APE1 enzymatic activity on this DNA lesion. By using orthogonal approaches, we found that: (i) the interaction between AUF1 and APE1 is modulated by HO-treatment; (ii) depletion of APE1 and AUF1 causes the accumulation of single- and double- strand breaks; and (iii) both proteins are involved in modulating the formation of DNA:RNA hybrids. These results establish unexpected functions of AUF1 in modulating genome stability and improve our knowledge of APE1 biology with respect to 8-oxo-guanosine embedded in DNA. By showing a novel function of AUF1, our findings shed new light on the process of genome stability in mammalian cells toward oxidative stress-related damages. 39, 411-431.

Citing Articles

Apurinic/Apyrimidinic Endodeoxyribonuclease 1 modulates RNA G-quadruplex folding of miR-92b and controls its expression in cancer cells.

Bellina A, Malfatti M, Salgado G, Fleming A, Antoniali G, Othman Z Proc Natl Acad Sci U S A. 2024; 121(46):e2317861121.

PMID: 39495925 PMC: 11572961. DOI: 10.1073/pnas.2317861121.

Emerging roles of bases modifications and DNA repair proteins in onco-miRNA processing: novel insights in cancer biology.

Mangiapane G, DAgostino V, Tell G Cancer Gene Ther. 2024; 31(12):1765-1772.

PMID: 39322751 DOI: 10.1038/s41417-024-00836-x.

Revisiting Two Decades of Research Focused on Targeting APE1 for Cancer Therapy: The Pros and Cons.

Malfatti M, Bellina A, Antoniali G, Tell G Cells. 2023; 12(14).

PMID: 37508559 PMC: 10378182. DOI: 10.3390/cells12141895.

References

Ishchenko A, Deprez E, Maksimenko A, Brochon J, Tauc P, Saparbaev M . Uncoupling of the base excision and nucleotide incision repair pathways reveals their respective biological roles. Proc Natl Acad Sci U S A. 2006; 103(8):2564-9. PMC: 1413785. DOI: 10.1073/pnas.0508582103. View

Malfatti M, Henneke G, Balachander S, Koh K, Newnam G, Uehara R . Unlike the counterpart, archaeal RNase HII cannot process ribose monophosphate abasic sites and oxidized ribonucleotides embedded in DNA. J Biol Chem. 2019; 294(35):13061-13072. PMC: 6721941. DOI: 10.1074/jbc.RA119.009493. View

Koh K, Chiu H, Riedo E, Storici F . Measuring the elasticity of ribonucleotide(s)-containing DNA molecules using AFM. Methods Mol Biol. 2015; 1297:43-57. DOI: 10.1007/978-1-4939-2562-9_3. View

Fantini D, Vascotto C, Marasco D, DAmbrosio C, Romanello M, Vitagliano L . Critical lysine residues within the overlooked N-terminal domain of human APE1 regulate its biological functions. Nucleic Acids Res. 2010; 38(22):8239-56. PMC: 3001066. DOI: 10.1093/nar/gkq691. View

Yoon J, De S, Srikantan S, Abdelmohsen K, Grammatikakis I, Kim J . PAR-CLIP analysis uncovers AUF1 impact on target RNA fate and genome integrity. Nat Commun. 2014; 5:5248. PMC: 4291169. DOI: 10.1038/ncomms6248. View

Perez-Riverol Y, Csordas A, Bai J, Bernal-Llinares M, Hewapathirana S, Kundu D . The PRIDE database and related tools and resources in 2019: improving support for quantification data. Nucleic Acids Res. 2018; 47(D1):D442-D450. PMC: 6323896. DOI: 10.1093/nar/gky1106. View

Promonet A, Padioleau I, Liu Y, Sanz L, Biernacka A, Schmitz A . Topoisomerase 1 prevents replication stress at R-loop-enriched transcription termination sites. Nat Commun. 2020; 11(1):3940. PMC: 7414224. DOI: 10.1038/s41467-020-17858-2. View

Vaisman A, McDonald J, Huston D, Kuban W, Liu L, Van Houten B . Removal of misincorporated ribonucleotides from prokaryotic genomes: an unexpected role for nucleotide excision repair. PLoS Genet. 2013; 9(11):e1003878. PMC: 3820734. DOI: 10.1371/journal.pgen.1003878. View

Codrich M, Comelli M, Malfatti M, Mio C, Ayyildiz D, Zhang C . Inhibition of APE1-endonuclease activity affects cell metabolism in colon cancer cells via a p53-dependent pathway. DNA Repair (Amst). 2019; 82:102675. PMC: 7092503. DOI: 10.1016/j.dnarep.2019.102675. View

10.

Agarwal P, Miller K . The nucleosome: orchestrating DNA damage signaling and repair within chromatin. Biochem Cell Biol. 2016; 94(5):381-395. DOI: 10.1139/bcb-2016-0017. View

11.

Hayakawa H, Fujikane A, Ito R, Matsumoto M, Nakayama K, Sekiguchi M . Human proteins that specifically bind to 8-oxoguanine-containing RNA and their responses to oxidative stress. Biochem Biophys Res Commun. 2010; 403(2):220-4. DOI: 10.1016/j.bbrc.2010.11.011. View

12.

Bindea G, Mlecnik B, Hackl H, Charoentong P, Tosolini M, Kirilovsky A . ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics. 2009; 25(8):1091-3. PMC: 2666812. DOI: 10.1093/bioinformatics/btp101. View

13.

Cristini A, Groh M, Kristiansen M, Gromak N . RNA/DNA Hybrid Interactome Identifies DXH9 as a Molecular Player in Transcriptional Termination and R-Loop-Associated DNA Damage. Cell Rep. 2018; 23(6):1891-1905. PMC: 5976580. DOI: 10.1016/j.celrep.2018.04.025. View

14.

Potenski C, Klein H . How the misincorporation of ribonucleotides into genomic DNA can be both harmful and helpful to cells. Nucleic Acids Res. 2014; 42(16):10226-34. PMC: 4176331. DOI: 10.1093/nar/gku773. View

15.

Mohanty B, Karam J, Howley B, Dalton A, Grelet S, Dincman T . Heterogeneous nuclear ribonucleoprotein E1 binds polycytosine DNA and monitors genome integrity. Life Sci Alliance. 2021; 4(9). PMC: 8321654. DOI: 10.26508/lsa.202000995. View

16.

Poletto M, Vascotto C, Scognamiglio P, Lirussi L, Marasco D, Tell G . Role of the unstructured N-terminal domain of the hAPE1 (human apurinic/apyrimidinic endonuclease 1) in the modulation of its interaction with nucleic acids and NPM1 (nucleophosmin). Biochem J. 2013; 452(3):545-57. DOI: 10.1042/BJ20121277. View

17.

Ide H, Nakano T, Salem A, Shoulkamy M . DNA-protein cross-links: Formidable challenges to maintaining genome integrity. DNA Repair (Amst). 2018; 71:190-197. DOI: 10.1016/j.dnarep.2018.08.024. View

18.

Meroni A, Mentegari E, Crespan E, Muzi-Falconi M, Lazzaro F, Podesta A . The Incorporation of Ribonucleotides Induces Structural and Conformational Changes in DNA. Biophys J. 2017; 113(7):1373-1382. PMC: 5627062. DOI: 10.1016/j.bpj.2017.07.013. View

19.

Liu H, Zheng W, Song Z . circDlgap4 Alleviates Cerebral Ischaemic Injury by Binding to AUF1 to Suppress Oxidative Stress and Neuroinflammation. Mol Neurobiol. 2022; 59(5):3218-3232. DOI: 10.1007/s12035-022-02796-5. View

20.

Cai Y, Geacintov N, Broyde S . Ribonucleotides as nucleotide excision repair substrates. DNA Repair (Amst). 2013; 13:55-60. PMC: 4371527. DOI: 10.1016/j.dnarep.2013.10.010. View