The mechanism of gap creation by a multifunctional nuclease during base excision repair

Jungmin Yoo, Donghun Lee, Hyeryeon Im, Sangmi Ji, Sanghoon Oh, Minsang Shin, Daeho Park, Gwangrog Lee

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

During base excision repair, a transient single-stranded DNA (ssDNA) gap is produced at the apurinic/apyrimidinic (AP) site. Exonuclease III, capable of performing both AP endonuclease and exonuclease activity, are responsible for gap creation in bacteria. We used single-molecule fluorescence resonance energy transfer to examine the mechanism of gap creation. We found an AP site anchor-based mechanism by which the intrinsically distributive enzyme binds strongly to the AP site and becomes a processive enzyme, rapidly creating a gap and an associated transient ssDNA loop. The gap size is determined by the rigidity of the ssDNA loop and the duplex stability of the DNA and is limited to a few nucleotides to maintain genomic stability. When the 3′ end is released from the AP endonuclease, polymerase I quickly initiates DNA synthesis and fills the gap. Our work provides previously unidentified insights into how a signal of DNA damage changes the enzymatic functions.

Original languageEnglish
Article numbereabg0076
JournalScience advances
Volume7
Issue number29
DOIs
StatePublished - Jul 2021

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