期刊
BIOCHEMISTRY
卷 48, 期 46, 页码 10858-10865出版社
AMER CHEMICAL SOC
DOI: 10.1021/bi901373e
关键词
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资金
- BBSRC
- Wellcome Trust [069399/Z/02]
- MRC [G0400534]
- MRC [G0400534] Funding Source: UKRI
- Medical Research Council [G0400534] Funding Source: researchfish
It has been proposed that human telomerase RNA (hTR) interacts with dyskerin, prior to assembly of the telomerase holoenzyme. The direct interaction of dyskerin and hTR has not been demonstrated and is an experimentally challenging research problem because of difficulties in expressing and purifying dyskerin in quantities that are useful for biophysical analysis. By orthogonally labeling dyskerin and hTR, we have been able to employ single-molecule two-color coincidence detection (TCCD) to observe directly the formation of a dyskerin center dot hTR complex. By systematic deletion of hTR subdomains, we have gained insights into the RNA sites required for interaction with dyskerin. We then investigated mutated forms of hTR and dyskerin that are associated with dyskeratosis congenita (DC), on the basis of clinical genetics studies, for their effects on the dyskerin center dot hTR interaction. Dyskerin mutations associated with X-linked DC resulted in significant impairment of the dyskerin center dot hTR interaction, whereas mutations in hTR associated with autosomal dominant (AD) DC did not affect the interaction. We propose that disruption of the dyskerin center dot hTR interaction may contribute to X-linked DC.
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