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How the human telomeric proteins TRF1 and TRF2 recognize telomeric DNA: a view from high‐resolution crystal structures
Author(s) -
Court Robert,
Chapman Lynda,
Fairall Louise,
Rhodes Daniela
Publication year - 2005
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400314
Subject(s) - telomere , dna , biology , telomere binding protein , dna binding protein , shelterin , tandem repeat , helix (gastropod) , binding site , plasma protein binding , biophysics , genetics , microbiology and biotechnology , gene , genome , transcription factor , ecology , snail
Human telomeres consist of tandem arrays of TTAGGG sequence repeats that are specifically bound by two proteins, TRF1 and TRF2. They bind to DNA as preformed homodimers and have the same architecture in which the DNA‐binding domains (Dbds) form independent structural units. Despite these similarities, TRF1 and TRF2 have different functions at telomeres. The X‐ray crystal structures of both TRF1‐ and TRF2‐Dbds in complex with telomeric DNA (2.0 and 1.8 Å resolution, respectively) show that they recognize the same TAGGGTT binding site by means of homeodomains, as does the yeast telomeric protein Rap1p. Two of the three G‐C base pairs that characterize telomeric repeats are recognized specifically and an unusually large number of water molecules mediate protein–DNA interactions. The binding of the TRF2‐Dbd to the DNA double helix shows no distortions that would account for the promotion of t‐loops in which TRF2 has been implicated.