Telomere proteins POT1, TRF1 and TRF2 augment long-patch base excision repair in vitro |
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| Authors: | Adam S Miller Lata Balakrishnan Noah A Buncher Patricia L Opresko Robert A Bambara |
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| Affiliation: | 1.Department of Biochemistry and Biophysics; University of Rochester School of Medicine and Dentistry; Rochester, NY USA;2.Department of Environmental and Occupational Health; University of Pittsburgh Graduate School of Public Health; Pittsburgh, PA USA |
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| 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.Key words: telomeres, base excision repair, shelterin complex, oxidative damage, LP-BER |
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