title: Telomere proteins POT1, TRF1 and TRF2 augment long-patch base excision repair in vitro.
abstract: Human telomeres consist of multiple tandem hexameric repeats, each containing a guanine triplet. Guanosine-rich clusters are highly susceptible to oxidative base damage, necessitating base excision repair (BER). Previous demonstration of enhanced strand displacement synthesis by the BER component DNA polymerase β in the presence of telomere protein TRF2 suggests that telomeres employ long-patch (LP) BER. Earlier analyses in vitro showed that efficiency of BER reactions is reduced in the DNA-histone environment of chromatin. Evidence presented here indicates that BER is promoted at telomeres. We found that the three proteins that contact telomere DNA, POT1, TRF1 and TRF2, enhance the rate of individual steps of LP-BER and stimulate the complete reconstituted LP-BER pathway. Thought to protect telomere DNA from degradation, these proteins still apparently evolved to allow selective access of repair proteins.
authors.affiliation: Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
authors.forename: Adam S
authors.initials: AS
authors.lastname: Miller
authors.forename: Lata
authors.initials: L
authors.lastname: Balakrishnan
authors.forename: Noah A
authors.initials: NA
authors.lastname: Buncher
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Opresko
authors.forename: Robert A
authors.initials: RA
authors.lastname: Bambara
mesh_terms: D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000378:metabolism; D019951:DNA Polymerase beta / Q000378:metabolism; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D045585:Flap Endonucleases / Q000378:metabolism; D006801:Humans; D011485:Protein Binding; D000089804:Shelterin Complex; D013379:Substrate Specificity; D016615:Telomere / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000378:metabolism*; D035321:Telomeric Repeat Binding Protein 1 / Q000378:metabolism*; D035341:Telomeric Repeat Binding Protein 2 / Q000378:metabolism*
chemical_list: C440849:POT1 protein, human; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; D035321:Telomeric Repeat Binding Protein 1; D035341:Telomeric Repeat Binding Protein 2; D019951:DNA Polymerase beta; D045585:Flap Endonucleases; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D011088:DNA Ligases; D000072481:DNA Ligase ATP