RT Journal Article
SR Electronic
T1 A genome wide dosage suppressor network reveals genetic robustness and a novel mechanism for Huntington’s disease
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 000265
DO 10.1101/000265
A1 Biranchi Patra
A1 Yoshiko Kon
A1 Gitanjali Yadav
A1 Anthony W. Sevold
A1 Jesse P. Frumkin
A1 Ravishankar R. Vallabhajosyula
A1 Arend Hintze
A1 Bjørn Østman
A1 Jory Schossau
A1 Ashish Bhan
A1 Bruz Marzolf
A1 Jenna K. Tamashiro
A1 Amardeep Kaur
A1 Nitin S. Baliga
A1 Elizabeth J. Grayhack
A1 Christoph Adami
A1 David J. Galas
A1 Alpan Raval
A1 Eric M. Phizicky
A1 Animesh Ray
YR 2013
UL http://biorxiv.org/content/early/2013/11/11/000265.abstract
AB Mutational robustness is the extent to which an organism has evolved to withstand the effects of deleterious mutations. We explored the extent of mutational robustness in the budding yeast by genome wide dosage suppressor analysis of 53 conditional lethal mutations in cell division cycle and RNA synthesis related genes, revealing 660 suppressor interactions of which 642 are novel. This collection has several distinctive features, including high co-occurrence of mutant-suppressor pairs within protein modules, highly correlated functions between the pairs, and higher diversity of functions among the co-suppressors than previously observed. Dosage suppression of essential genes encoding RNA polymerase subunits and chromosome cohesion complex suggest a surprising degree of functional plasticity of macromolecular complexes and the existence of degenerate pathways for circumventing potentially lethal mutations. The utility of dosage-suppressor networks is illustrated by the discovery of a novel connection between chromosome cohesion-condensation pathways involving homologous recombination, and Huntington’s disease.