encodes a novel low-molecular-weight GTPase, and 
pirn 1 encodes the respective GTP exchange factor. 
Recent work has shown that the piml product is a 
highly abundant chromatin protein that is present at 
approximately one molecule for every four nucleo- 
somes. Cells that lack either piml or spil gene 
function enter mitosis without completing DNA rep- 
lication. Thus it is assumed that piml /spil com- 
prise a chromatin-sensing mechanism that signals 
the state of the genome to the mitotic regulatory 
apparatus. Currently the effector mechanism of 
piml /spil is being investigated. This pathway in- 
volves other genes, specifically pim2 and dis2, that 
encode the type 1 protein phosphatase. 
The Gi phase of the fission yeast cell cycle is also a 
subject of investigation. Two new genes, sdclO and 
cdtl, have been identified. The sdclO gene inter- 
acts with the previously known cdclO gene to form 
a cell cycle transcription factor that activates genes 
required for DNA replication. The most critical of 
these is cdtl, overexpression of which essentially 
ablates the Gj phase of the cell cycle. Under some 
conditions this effect is lethal, because the cell pro- 
gresses through the division cycle faster than ade- 
quate cell growth can occur. The precise biochemi- 
cal function of the cdtl product is unknown and is 
currently under study. 
Mammalian Cell Cycle Control 
Dr. Beach's laboratory previously described a new 
class of cyclins known as D-type cyclins. In humans 
there are three such cyclins that display striking tis- 
sue-specific expression. Cyclin Dl , which was inde- 
pendently discovered by several research groups, is 
also known as PRADl or the Bcl-1 oncogene. To 
date, cyclin Dl is the only cyclin that has been com- 
pellingly linked to human disease. To investigate 
the possibility that cyclin D2 or D3 might be in- 
volved in oncogenesis. Dr. Beach and his colleagues 
collaborated with Dr. David Ward (Yale University) 
in mapping the location of these genes in the human 
genome to 12pl3 (D2) and 6p21 (D3). DNA rear- 
rangements at these loci have been implicated in a 
variety of tumor types, and studies are under way to 
test whether cyclin D2 or D3 is the active oncogene 
in these tumors. 
Further studies have focused on the biological 
function of the D-type cyclins. These cyclins asso- 
ciate with at least three protein kinase catalytic sub- 
units (CDK2, 4, and 5) although the relevant pro- 
tein substrates are presently unknown. Several 
additional proteins with which D cyclins associate 
in the cell have been identified. One is a factor that 
is essential for DNA replication. This observation di- 
rectly links the D cyclins with other elements of the 
cell cycle control pathways and strongly hints that 
they act at the Gj/S stage of the cycle. 
Recently it has become apparent that the tumor- 
suppressor protein p53 acts as a cell cycle check- 
point regulator. In particular, cells that lack normal 
p53 function do not arrest in the division cycle in 
response to damaging agents such as 7 irradiation. 
Although it is likely that p53 acts as a transcription 
factor, it is not known which gene(s) is the critical 
target of p53 function. To address this issue Dr. 
Beach's laboratory again made use of the fission 
yeast model organism. Overexpression of p53 
causes cell cycle arrest in fission yeast, as it does in 
human cells. Yeast mutants that are resistant to p53 
overexpression were generated. In these mutants 
the p53 protein itself is unaffected, but the cell is 
relatively unresponsive to p53 cell cycle inhibition. 
It is hoped that these mutants will lead to the identi- 
fication of p53 target genes in yeast and thereafter in 
human cells. 
Fission Yeast Genome Mapping 
Dr. Beach's laboratory undertook to develop a 
high-resolution physical map of the 1 5-Mb genome 
of the fission yeast. This objective has largely been 
accomplished: 1,920 cosmid clones have been as- 
sembled into ~30 contigs that comprise almost the 
entire genome. Each of the NotI and Sfil sites in the 
genome have been identified in the cosmids, and 
~200 genes have been mapped. The resolution of 
the genome map presently stands at 1 0 kb. The exis- 
tence of the ordered set of fission yeast cosmids 
renders obsolete the mapping of genes by classical 
genetic methods. 
The fission yeast genome mapping project is sup- 
ported by funds from the National Institutes of 
Health. 
Dr. Beach is also Senior Staff Scientist at Cold 
Spring Harbor Laboratory and Adjunct Associate 
Professor of Microbiology at the State University 
of New York at Stony Brook. 
Articles 
Bischofif, J R., Casso, D., and Beach, D. 1992. Hu- 
man p53 inhibits growth in Schizosaccharo- 
myces pombe. Mol Cell Biol 12:1 405- 1411. 
DeVoti, J., Seydoux, G., Beach, D., and McLeod, M. 
1991. Interaction between rani* protein kinase 
and cAMP dependent protein kinase as negative 
regulators of fission yeast meiosis. EMBO J 
10:3759-3768. 
Galaktionov, K., and Beach, D. 1991. Specific acti- 
CELL BIOLOGY AND REGULATION 
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