What question did this study set out to answer?

To determine how mutations at the conserved active site residue Valine 867 in human telomerase reverse transcriptase affect catalytic activity, processivity, and nucleotide incorporation fidelity.

January 30, 2007Nucleic Acids ResearchOpen Access

The active site residue Valine 867 in human telomerase reverse transcriptase influences nucleotide incorporation and fidelity

View Full Paper

Ask AI

Bookmark

To determine how mutations at the conserved active site residue Valine 867 in human telomerase reverse transcriptase affect catalytic activity, processivity, and nucleotide incorporation fidelity.
Generated site-directed substitutions at Valine 867 (Ala, Met, and Thr) within the conserved C motif of human telomerase reverse transcriptase (hTERT).
Reconstituted mutant hTERT proteins with wild-type and template-mutated telomerase RNAs to evaluate repeat extension rate, processivity, and template-copying defects.
Measured nucleotide incorporation fidelity across template positions for wild-type and mutant telomerase complexes.
All tested Val867 substitutions (Ala, Met, Thr) reduced telomere repeat extension rates to approximately 20% to 50% of the wild-type rate while minimally altering polymerase processivity.
Reconstitution of the V867M mutant with mutated RNA templates revealed that reduced extension rates stemmed specifically from a defect in copying template adenine residues.
Val867 substitutions consistently displayed increased nucleotide incorporation fidelity compared to wild-type hTERT.

Discussion

No takes yet. Share an insight, caveat, or question.

Implication

Biochemical assays show that Val867 substitutions decrease elongation speed but increase accuracy in human telomerase, suggesting an evolutionary trade-off between catalytic rate and fidelity.

Cite This Study

Drosopoulos et al. (2007) studied this question.

synapsesocial.com/papers/6a7724337d04941475ae2b7c https://doi.org/10.1093/nar/gkm002

View Full Paper

Ask AI

Bookmark

Implication

Biochemical assays show that Val867 substitutions decrease elongation speed but increase accuracy in human telomerase, suggesting an evolutionary trade-off between catalytic rate and fidelity.

The active site residue Valine 867 in human telomerase reverse transcriptase influences nucleotide incorporation and fidelity

Key Points

Discussion

Implication

Cite This Study

The active site residue Valine 867 in human telomerase reverse transcriptase influences nucleotide incorporation and fidelity

Key Points

Discussion

Implication

Cite This Study

Also Consider

Also Consider