Download Shwachman-Diamond syndrome (SDS) is an autosomal recessive

CELLULAR AND MOLECULAR BIOLOGY
RPL46A Does Not Compensate the Growth Defect Caused by Deletion of SDO1, a Yeast
Homolog of the Human Shwachman-Diamond Syndrome Gene. KATHARINA HOPP,
Department of Biology, Brescia University, Owensboro, KY 42301.
Shwachman-Diamond syndrome (SDS) is an autosomal recessive disorder that
causes bone marrow failure, exocrine pancreatic insufficiency, and congenital anomalies.
SDS is associated with mutations of the SBDS gene on chromosome 7. Mutations in the
yeast homolog of SBDS, SDO1, effect ribosomal RNA processing, indicting a role for the
Sdo1 protein in ribosome synthesis. Polysome profiles of SDO1- null cells showed halfmer polysomes, which are characteristic of cells with a 60S subunits deficit.
Surprisingly, however, these cells show relatively high levels of free 60S subunits
suggesting instead that there is a defect in subunit joining during the initiation phase of
translation. The growth defect of SDO1-null strains can be suppressed by mutations
elsewhere in the yeast genome. Polysome profiles of an isolated suppressor locus
showed a decrease in 60S subunits. This observation led to the hypothesis that
phenotypes associated with the SDO1-null mutation can be compensated by a mutation
that decreases the level of 60S subunits. To test this hypothesis a strain with the SDO1null allele and a second mutation in the RPL 46A locus, which is known to reduce 60S
ribosomal subunits, was created. The SDO1/RPL46 double mutant did not show the
anticipated suppressor phenotype. Thus, a general reduction in 60S ribosomal subunits
does not compensate for the absence of functional Sdo1. Further research is currently
focused on identifying the suppressor locus by screening with a wild-type yeast genomic
library.