REGULATION OF APE1 BY NEIL3 ZINC FINGER-GRF REPEAT ON SINGLE-STRANDED DNA

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Ha, A. (2020). REGULATION OF APE1 BY NEIL3 ZINC FINGER-GRF REPEAT ON SINGLE-STRANDED DNA. Unc Charlotte Electronic Theses And Dissertations.
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Abstract

Base excision repair (BER) is a critical pathway in repairing single base lesions caused by oxidation, deamination, and alkylation. NEIL3 is a DNA glycosylase which functions in initiating BER pathway by recognizing and removing damaged bases. Although there have been many studies reported on the function of NEIL3 in BER, the potential role of NEIL3 in the regulation of downstream BER players such as APE1 have not been dissected yet. In comparison to other Fpg/Nei glycosylase family members including NEIL1 and NEIL2, NEIL3 has two distinct zinc finger GRF motifs (Zf-GRF) in extreme C-terminus. In my thesis, two NEIL3 Zf-GRF motifs are my main focus due to their highly conserved residues across multiple vertebrates. Remarkably, my experimental observations reveal unexpected findings that two NEIL3 Zf-GRF motifs but not one Zf-GRF motif can interact and regulate APE1’s endonuclease activity. In particular, I have demonstrated (1) two NEIL3 Zf-GRF motifs associate with APE1 but not APE2, (2) NEIL3 Zf-GRF motifs bind to single-stranded DNA (ssDNA) in a sequence-independent manner, (3) two Zf-GRF motifs allow for binding to shorter ssDNA compared with one Zf-GRF motif, and (4) the Zf-GRF repeat within NEIL3 compromises APE1’s endonuclease activity on ssDNA. Taken together, my results suggest a distinct mechanism by which NEIL3 Zf-GRF repeat maintains genome stability of ssDNA via suppression of APE1 endonuclease activity-mediated DNA breaks.

Details
Author

Ha, Anh

Title

REGULATION OF APE1 BY NEIL3 ZINC FINGER-GRF REPEAT ON SINGLE-STRANDED DNA

Physical Description

1 online resource (54 pages) : PDF

Date

2020

Degree Granting Institution

University of North Carolina at Charlotte

Abstract

Base excision repair (BER) is a critical pathway in repairing single base lesions caused by oxidation, deamination, and alkylation. NEIL3 is a DNA glycosylase which functions in initiating BER pathway by recognizing and removing damaged bases. Although there have been many studies reported on the function of NEIL3 in BER, the potential role of NEIL3 in the regulation of downstream BER players such as APE1 have not been dissected yet. In comparison to other Fpg/Nei glycosylase family members including NEIL1 and NEIL2, NEIL3 has two distinct zinc finger GRF motifs (Zf-GRF) in extreme C-terminus. In my thesis, two NEIL3 Zf-GRF motifs are my main focus due to their highly conserved residues across multiple vertebrates. Remarkably, my experimental observations reveal unexpected findings that two NEIL3 Zf-GRF motifs but not one Zf-GRF motif can interact and regulate APE1’s endonuclease activity. In particular, I have demonstrated (1) two NEIL3 Zf-GRF motifs associate with APE1 but not APE2, (2) NEIL3 Zf-GRF motifs bind to single-stranded DNA (ssDNA) in a sequence-independent manner, (3) two Zf-GRF motifs allow for binding to shorter ssDNA compared with one Zf-GRF motif, and (4) the Zf-GRF repeat within NEIL3 compromises APE1’s endonuclease activity on ssDNA. Taken together, my results suggest a distinct mechanism by which NEIL3 Zf-GRF repeat maintains genome stability of ssDNA via suppression of APE1 endonuclease activity-mediated DNA breaks.

Genre

masters theses

Subjects--Topics

Molecular biology
Cytology

Degree

M.S.

Keywords

Ape1
Base Excision Repair
GRF
Single Stranded Dna
Zinc Finger

Subject Area

Biology

Advisor(s)

Yan, Shan

Committee Members

Richardson, Christine
Tomida, Junya

Degree Note

Thesis (M.S.)--University of North Carolina at Charlotte, 2020.

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Rights Holder Information

Copyright is held by the author unless otherwise indicated.

Identifier

Ha_uncc_0694N_12385

Permalink

http://hdl.handle.net/20.500.13093/etd:2419