Genetics, volume 208, issue 1, pages 97-110
Using Separation-of-Function Mutagenesis To Define the Full Spectrum of Activities Performed by the Est1 Telomerase Subunit in Vivo
1
Division of Biological Sciences, University of California, San Diego, La Jolla, California 92093-0130
|
2
Salk Institute for Biological Studies, La Jolla, California 92037-1099
|
Publication type: Journal Article
Publication date: 2018-01-01
PubMed ID:
29187507
Genetics
Abstract
A leading objective in biology is to identify the complete set of activities performed by each gene. Identification of a comprehensive set of separation...
A leading objective in biology is to identify the complete set of activities that each gene performs in vivo. In this study, we have asked whether a genetic approach can provide an efficient means of achieving this goal, through the identification and analysis of a comprehensive set of separation-of-function (sof−) mutations in a gene. Toward this goal, we have subjected the Saccharomyces cerevisiae EST1 gene, which encodes a regulatory subunit of telomerase, to intensive mutagenesis (with an average coverage of one mutation for every 4.5 residues), using strategies that eliminated those mutations that disrupted protein folding/stability. The resulting set of sof− mutations defined four biochemically distinct activities for the Est1 telomerase protein: two temporally separable steps in telomerase holoenzyme assembly, a telomerase recruitment activity, and a fourth newly discovered regulatory function. Although biochemically distinct, impairment of each of these four different activities nevertheless conferred a common phenotype (critically short telomeres) comparable to that of an est1-∆ null strain. This highlights the limitations of gene deletions, even for nonessential genes; we suggest that employing a representative set of sof− mutations for each gene in future high- and low-throughput investigations will provide deeper insights into how proteins interact inside the cell.
Citations by journals
|
1
|
|
|
Scientific Reports
|
Scientific Reports
1 publication, 16.67%
|
|
International Journal of Molecular Sciences
|
International Journal of Molecular Sciences
1 publication, 16.67%
|
|
PLoS Genetics
|
PLoS Genetics
1 publication, 16.67%
|
|
Nucleic Acids Research
|
Nucleic Acids Research
1 publication, 16.67%
|
|
1
|
Citations by publishers
|
1
|
|
|
Springer Nature
|
Springer Nature
1 publication, 16.67%
|
|
Multidisciplinary Digital Publishing Institute (MDPI)
|
Multidisciplinary Digital Publishing Institute (MDPI)
1 publication, 16.67%
|
|
Public Library of Science (PLoS)
|
Public Library of Science (PLoS)
1 publication, 16.67%
|
|
Oxford University Press
|
Oxford University Press
1 publication, 16.67%
|
|
1
|
- We do not take into account publications that without a DOI.
- Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
- Statistics recalculated weekly.
{"yearsCitations":{"type":"bar","data":{"show":true,"labels":[2019,2020,2021,2022,2023],"ids":[0,0,0,0,0],"codes":[0,0,0,0,0],"imageUrls":["","","","",""],"datasets":[{"label":"Citations number","data":[1,2,0,1,2],"backgroundColor":["#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6"],"percentage":["16.67","33.33",0,"16.67","33.33"],"barThickness":null}]},"options":{"indexAxis":"x","maintainAspectRatio":true,"scales":{"y":{"ticks":{"precision":0,"autoSkip":false,"font":{"family":"Montserrat"},"color":"#000000"}},"x":{"ticks":{"stepSize":1,"precision":0,"font":{"family":"Montserrat"},"color":"#000000"}}},"plugins":{"legend":{"position":"top","labels":{"font":{"family":"Montserrat"},"color":"#000000"}},"title":{"display":true,"text":"Citations per year","font":{"size":24,"family":"Montserrat","weight":600},"color":"#000000"}}}},"journals":{"type":"bar","data":{"show":true,"labels":["Scientific Reports","International Journal of Molecular Sciences","PLoS Genetics","Nucleic Acids Research"],"ids":[13767,14627,785,23904],"codes":[0,0,0,0],"imageUrls":["\/storage\/images\/resized\/voXLqlsvTwv5p3iMQ8Dhs95nqB4AXOG7Taj7G4ra_medium.webp","\/storage\/images\/resized\/MjH1ITP7lMYGxeqUZfkt2BnVLgjkk413jwBV97XX_medium.webp","\/storage\/images\/resized\/PRGhlgB4OKRltSNtT39eA6wlnOTGRap1QQ6FQHih_medium.webp","\/storage\/images\/resized\/yNSijlgQghQF53VZuyFLA30CKDe4j3HK74Vtpnxa_medium.webp"],"datasets":[{"label":"","data":[1,1,1,1],"backgroundColor":["#3B82F6","#3B82F6","#3B82F6","#3B82F6"],"percentage":[16.67,16.67,16.67,16.67],"barThickness":13}]},"options":{"indexAxis":"y","maintainAspectRatio":false,"scales":{"y":{"ticks":{"precision":0,"autoSkip":false,"font":{"family":"Montserrat"},"color":"#000000"}},"x":{"ticks":{"stepSize":null,"precision":0,"font":{"family":"Montserrat"},"color":"#000000"}}},"plugins":{"legend":{"position":"top","labels":{"font":{"family":"Montserrat"},"color":"#000000"}},"title":{"display":true,"text":"Journals","font":{"size":24,"family":"Montserrat","weight":600},"color":"#000000"}}}},"publishers":{"type":"bar","data":{"show":true,"labels":["Springer Nature","Multidisciplinary Digital Publishing Institute (MDPI)","Public Library of Science (PLoS)","Oxford University Press"],"ids":[8,202,344,19],"codes":[0,0,0,0],"imageUrls":["\/storage\/images\/resized\/voXLqlsvTwv5p3iMQ8Dhs95nqB4AXOG7Taj7G4ra_medium.webp","\/storage\/images\/resized\/MjH1ITP7lMYGxeqUZfkt2BnVLgjkk413jwBV97XX_medium.webp","\/storage\/images\/resized\/PRGhlgB4OKRltSNtT39eA6wlnOTGRap1QQ6FQHih_medium.webp","\/storage\/images\/resized\/yNSijlgQghQF53VZuyFLA30CKDe4j3HK74Vtpnxa_medium.webp"],"datasets":[{"label":"","data":[1,1,1,1],"backgroundColor":["#3B82F6","#3B82F6","#3B82F6","#3B82F6"],"percentage":[16.67,16.67,16.67,16.67],"barThickness":13}]},"options":{"indexAxis":"y","maintainAspectRatio":false,"scales":{"y":{"ticks":{"precision":0,"autoSkip":false,"font":{"family":"Montserrat"},"color":"#000000"}},"x":{"ticks":{"stepSize":null,"precision":0,"font":{"family":"Montserrat"},"color":"#000000"}}},"plugins":{"legend":{"position":"top","labels":{"font":{"family":"Montserrat"},"color":"#000000"}},"title":{"display":true,"text":"Publishers","font":{"size":24,"family":"Montserrat","weight":600},"color":"#000000"}}}}}
Metrics
Cite this
GOST |
RIS |
BibTex |
MLA
Cite this
GOST
Copy
Lubin J. W. et al. Using Separation-of-Function Mutagenesis To Define the Full Spectrum of Activities Performed by the Est1 Telomerase Subunit in Vivo // Genetics. 2018. Vol. 208. No. 1. pp. 97-110.
GOST all authors (up to 50)
Copy
Lubin J. W., Tucey T. M., Lundblad V. Using Separation-of-Function Mutagenesis To Define the Full Spectrum of Activities Performed by the Est1 Telomerase Subunit in Vivo // Genetics. 2018. Vol. 208. No. 1. pp. 97-110.
Cite this
RIS
Copy
TY - JOUR
DO - 10.1534/genetics.117.300145
UR - https://doi.org/10.1534%2Fgenetics.117.300145
TI - Using Separation-of-Function Mutagenesis To Define the Full Spectrum of Activities Performed by the Est1 Telomerase Subunit in Vivo
T2 - Genetics
AU - Lubin, Johnathan W
AU - Tucey, Timothy M
AU - Lundblad, Victoria
PY - 2018
DA - 2018/01/01 00:00:00
PB - Genetics Society of America
SP - 97-110
IS - 1
VL - 208
PMID - 29187507
SN - 0016-6731
SN - 1943-2631
ER -
Cite this
BibTex
Copy
@article{2018_Lubin,
author = {Johnathan W Lubin and Timothy M Tucey and Victoria Lundblad},
title = {Using Separation-of-Function Mutagenesis To Define the Full Spectrum of Activities Performed by the Est1 Telomerase Subunit in Vivo},
journal = {Genetics},
year = {2018},
volume = {208},
publisher = {Genetics Society of America},
month = {jan},
url = {https://doi.org/10.1534%2Fgenetics.117.300145},
number = {1},
pages = {97--110},
doi = {10.1534/genetics.117.300145}
}
Cite this
MLA
Copy
Lubin, Johnathan W., et al. “Using Separation-of-Function Mutagenesis To Define the Full Spectrum of Activities Performed by the Est1 Telomerase Subunit in Vivo.” Genetics, vol. 208, no. 1, Jan. 2018, pp. 97-110. https://doi.org/10.1534%2Fgenetics.117.300145.