Intron-encoded homing endonuclease I-TevI also functions as a transcriptional autorepressor

Nat Struct Mol Biol. 2004 Oct;11(10):936-44. doi: 10.1038/nsmb823. Epub 2004 Sep 7.

Abstract

Customary binding sites of intron-encoded homing endonucleases lie within cognate intronless alleles, at the so-called homing sites. Here, we describe a novel, high-affinity binding site for I-TevI endonuclease, encoded within the group I td intron of phage T4. This site is an operator that overlaps the T4 late promoter, which drives I-TevI expression from within the td intron. I-TevI binds the operator and homing sites with equal affinity, and functions as a transcriptional autorepressor. Distinct sequence and spacing requirements of the catalytic domain result in reduced cleavage activity on operator DNA. Crystallographic studies showed that the overall interactions of the DNA-binding domain with the operator and homing sites are similar, but have some different hydrogen-bonding contacts. We present a model in which the flexibility in protein-DNA interactions allows I-TevI to bind variant intronless alleles to promote intron mobility while facilitating its function in autorepression, and thereby persistence in its host.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • DNA Footprinting
  • Electrophoretic Mobility Shift Assay
  • Endodeoxyribonucleases / genetics
  • Endodeoxyribonucleases / physiology*
  • Introns*
  • Molecular Sequence Data
  • Oligonucleotides
  • Promoter Regions, Genetic
  • Repressor Proteins / genetics
  • Repressor Proteins / physiology*
  • Sequence Homology, Nucleic Acid

Substances

  • Oligonucleotides
  • Repressor Proteins
  • Endodeoxyribonucleases
  • I-TEVI endonuclease

Associated data

  • PDB/1T2T