Sequential and Multistep Substrate Interrogation Provides the Scaffold for Specificity in Human Flap Endonuclease 1
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KAUST Department
Biological and Environmental Sciences and Engineering (BESE) DivisionBioscience Program
Enrichment Program
Laboratory of DNA Replication and Recombination
Physical Science and Engineering (PSE) Division
Date
2013-06-06Online Publication Date
2013-06-06Print Publication Date
2013-06Permanent link to this record
http://hdl.handle.net/10754/334510Metadata
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Human flap endonuclease 1 (FEN1), one of the structure-specific 5' nucleases, is integral in replication, repair, and recombination of cellular DNA. The 5' nucleases share significant unifying features yet cleave diverse substrates at similar positions relative to 5' end junctions. Using single-molecule Förster resonance energy transfer, we find a multistep mechanism that verifies all substrate features before inducing the intermediary-DNA bending step that is believed to unify 5' nuclease mechanisms. This is achieved by coordinating threading of the 5' flap of a nick junction into the conserved capped-helical gateway, overseeing the active site, and bending by binding at the base of the junction. We propose that this sequential and multistep substrate recognition process allows different 5' nucleases to recognize different substrates and restrict the induction of DNA bending to the last common step. Such mechanisms would also ensure the protection ofDNA junctions from nonspecific bending and cleavage. 2013 The Authors.Citation
Sobhy MA, Joudeh LI, Huang X, Takahashi M, Hamdan SM (2013) Sequential and Multistep Substrate Interrogation Provides the Scaffold for Specificity in Human Flap Endonuclease 1. Cell Reports 3: 1785-1794. doi:10.1016/j.celrep.2013.05.001.Publisher
Elsevier BVJournal
Cell ReportsPubMed ID
23746444Scopus Count
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