PMID- 18319724
OWN - NLM
STAT- MEDLINE
DCOM- 20080505
LR  - 20211020
IS  - 1744-4292 (Electronic)
IS  - 1744-4292 (Linking)
VI  - 4
DP  - 2008
TI  - A systems-level approach to mapping the telomere length maintenance gene 
      circuitry.
PG  - 172
LID - 10.1038/msb.2008.13 [doi]
AB  - The ends of eukaryotic chromosomes are protected by telomeres, nucleoprotein 
      structures that are essential for chromosomal stability and integrity. 
      Understanding how telomere length is controlled has significant medical 
      implications, especially in the fields of aging and cancer. Two recent systematic 
      genome-wide surveys measuring the telomere length of deleted mutants in the yeast 
      Saccharomyces cerevisiae have identified hundreds of telomere length maintenance 
      (TLM) genes, which span a large array of functional categories and different 
      localizations within the cell. This study presents a novel general method that 
      integrates large-scale screening mutant data with protein-protein interaction 
      information to rigorously chart the cellular subnetwork underlying the function 
      investigated. Applying this method to the yeast telomere length control data, we 
      identify pathways that connect the TLM proteins to the telomere-processing 
      machinery, and predict new TLM genes and their effect on telomere length. We 
      experimentally validate some of these predictions, demonstrating that our method 
      is remarkably accurate. Our results both uncover the complex cellular network 
      underlying TLM and validate a new method for inferring such networks.
FAU - Shachar, Rafi
AU  - Shachar R
AD  - School of Computer Science, Tel Aviv University, Ramat Aviv, Israel.
FAU - Ungar, Lior
AU  - Ungar L
FAU - Kupiec, Martin
AU  - Kupiec M
FAU - Ruppin, Eytan
AU  - Ruppin E
FAU - Sharan, Roded
AU  - Sharan R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080304
PL  - Germany
TA  - Mol Syst Biol
JT  - Molecular systems biology
JID - 101235389
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - 0 (Telomere-Binding Proteins)
SB  - IM
MH  - Gene Expression Regulation, Fungal
MH  - Genome
MH  - Genome, Fungal
MH  - *Models, Genetic
MH  - Models, Statistical
MH  - Mutation
MH  - Phenotype
MH  - Probability
MH  - Saccharomyces cerevisiae/*genetics
MH  - Saccharomyces cerevisiae Proteins/physiology
MH  - Systems Biology
MH  - Telomere/*ultrastructure
MH  - Telomere-Binding Proteins/metabolism
PMC - PMC2290934
EDAT- 2008/03/06 09:00
MHDA- 2008/05/06 09:00
PMCR- 2008/03/04
CRDT- 2008/03/06 09:00
PHST- 2008/01/21 00:00 [received]
PHST- 2008/01/28 00:00 [accepted]
PHST- 2008/03/06 09:00 [pubmed]
PHST- 2008/05/06 09:00 [medline]
PHST- 2008/03/06 09:00 [entrez]
PHST- 2008/03/04 00:00 [pmc-release]
AID - msb200813 [pii]
AID - 10.1038/msb.2008.13 [doi]
PST - ppublish
SO  - Mol Syst Biol. 2008;4:172. doi: 10.1038/msb.2008.13. Epub 2008 Mar 4.