Thus the pattern of IRE-ABP expression is also con- 
sistent with its proposed role as a mediator of the 
adaptive response to glucose. The chronic effect of 
insulin on the expression of this protein may be me- 
diated at the transcriptional level. An IRE-ABP gene 
has been isolated to investigate this possibility. It 
will be interesting to determine whether IRE-ABP 
gene transcription is subject to autoregulation in re- 
sponse to insulin and/or refeeding. 
IRE-ABP Shares Binding Specificity 
with the Testis-determining Factor 
The laboratories of Drs. Peter Goodfellow and 
Robin Lovell-Badge identified SRY as the testis- 
determining region on the basis of genetic evidence. 
Several patients with an XY genotype who failed to 
differentiate to the male phenotype have mutations 
in the HMG box domain of SRY. Certain transgenic 
mice with an XX genotype that express the cloned 
Sry gene have a male phenotype. Thus this locus was 
presumed to be the locus responsible for initiation 
of testis formation in the developing embryo. Be- 
cause IRE-ABP was isolated on the basis of DNA bind- 
ing, Dr. Alexander-Bridges and her colleagues were 
able to demonstrate that derivatives of IRE-ABP or 
Sry that carried mutations associated with sex rever- 
sal did not bind DNA. 
Rat IRE-ABP showed markedly higher affinity for 
the IRE-A motif than mouse Sry, but the nucleotides 
contacted by these proteins were essentially identi- 
cal between these divergent family members. In col- 
laboration with the laboratory of Dr. David Page 
(HHMI, Massachusetts Institute of Technology), 
human SRY and IRE-ABP have been shown to bind 
IRE-A DNA with equal affinity. Studies in progress 
will examine derivatives of SRY that contain muta- 
tions identified in several sex-reversed patients with 
the goal of defining the spectrum of defects that are 
associated with sex reversal. 
Dr. Alexander- Bridges is also Assistant Profes- 
sor of Medicine at Harvard Medical School and 
Clinical Assistant at Massachusetts General Hospi- 
tal, Boston. 
Articles 
Alexander-Bridges, M., Buggs, C, Giere, L., De- 
naro, M. , Kahn , B . , White , M . , Sukhatme, V. , and 
Nasrin, N. 1992. Models of insulin action on met- 
abolic and groMT;h response genes. Mol Cell Bio- 
chem 109:99-105. 
Alexander-Bridges, M., Dugast, I., Ercolani, L., 
Kong, X.F., Giere, L., and Nasrin, N. 1992. Mul- 
tiple insulin-responsive elements regulate tran- 
scription of the GAPDH gene. Adv Enzyme Regul 
32:149-159. 
Alexander-Bridges, M., Ercolani, L., Kong, X.F., 
and Nasrin, N. 1992. Identification of a core mo- 
tif that is recognized by three members of the 
HMG class of transcriptional regulators: IRE-ABP, 
SRY, and TC¥-la. J Cell Biochem 48:129-135. 
Nasrin, N., Buggs, C, Kong, X.F., Carnazza, J., 
Goebl, M., and Alexander-Bridges, M. 1991. 
DNA-binding properties of the product of the 
testis-determining gene and a related protein. Na- 
ture 354:317-320. 
CELL CYCLE CONTROL 
David H. Beach, Ph.D., Investigator 
The research in Dr. Beach's laboratory is broadly 
divided into three project areas: 1) cell cycle con- 
trol in the fission yeast genetic model system, 2) cell 
cycle control in vertebrate cells, particularly hu- 
man, and 3) mapping of the fission yeast genome. 
Fission Yeast Cell Cycle Control 
Single-celled eukaryotes such as the fission yeast 
and budding yeast continue to provide the most 
readily accessible material for the discovery of new 
cell cycle control genes and elaboration of their 
physiological function. During the past year Dr. 
Beach's laboratory has continued to study the so- 
called cell cycle checkpoints of fission yeast. The 
division cycle consists of multiple essential events 
such as DNA replication, nuclear division, and cell 
division. Checkpoint controls ensure that one cell 
cycle process does not occur until a prior event is 
completed. For example, it is essential that cell divi- 
sion not occur until DNA synthesis and repair are 
fully executed. 
Dr. Beach and his colleagues previously identified 
two genes, piml and spil, that are critically in- 
volved in this checkpoint control. The spil gene 
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