activation of MyoD. Current efforts focus on identi- 
fying trans acting elements that integrate with these 
sequences. In worms, several maternal-effect mu- 
tants have been isolated by Dr. Jim Priess and his 
colleagues. These mutant embryos produce excess 
muscle from the wrong lineage. It is possible that 
they define elements involved in the segregation of 
myogenic potential to specific cells during early 
cleavage stages. In apparent contrast to worms, frogs 
seem to activate MyoD in all cells of the blastoderm; 
however, expression is stabilized only in those pre- 
sumptive mesodermal cells that become induced by 
vegetal inducing factors such as activin. Frogs also 
contain maternal MyoD mRNA, which, however, 
seems not to be crucial for subsequent myogenesis, 
as its destruction with antisense DNA results in nor- 
mal muscle gene activation. 
The ts4l Chinese Hamster Cell Cycle Mutant 
The ts4 1 mutation of Chinese hamster cells was 
first isolated and characterized by Drs. Joseph 
Hirschberg and Menasahe Marcus (1982), who 
showed that at nonpermissive temperature, cells ac- 
cumulate up to 16°C equivalents of DNA. Dr. Wein- 
traub and his colleagues have shown that the muta- 
tion is recessive and that at nonpermissive 
temperature cells replicate their genome normally 
but, instead of going on into G2, M, and G^, pass 
directly into a second S phase. This entry into a sec- 
ond S phase does not require serum, nor is it inhib- 
ited by G2 checkpoints or mitotic inhibitors. 
Temperature shift experiments suggest that the 
ts4 1 gene product participates in two functions in 
the cell cycle: entry into mitosis and inhibition of 
entry into S phase. The ts4l mutation seems to de- 
fine a new class of cell cycle mutant that couples the 
sequential events of DNA replication and mitosis. 
(This research was supported by a grant from the 
National Institutes of Health.) 
Dr. Weintraub is also Full Member in the Divi- 
sion of Basic Sciences at the Fred Hutchinson 
Cancer Research Center, Seattle. 
Articles 
Bengal, E., Ransone, L., Scharfmann, R., Dwarki, 
VJ., Tapscott, SJ., Weintraub, H., and Verma, 
I.M. 1992. Functional antagonism between c-Jun 
and MyoD proteins: a direct physical association. 
Ce// 68:507-519. 
Chen, L., Krause, M., Draper, B., Weintraub, H., 
and Fire, A. 1992. Body-wall muscle formation in 
Caenorhabditis elegans embryos that lack the 
myoD homolog hlh-1. Science 256:240-243. 
Davis, R.L., and Weintraub, H. 1992. Acquisition 
of myogenic specificity by replacement of three 
amino acid residues from MyoD into El 2. Science 
256:1027-1030. 
CHARACTERIZATION OF NEWLY ISOLATED DISEASE GENES 
Raymond L. White, Ph.D., Investigator 
Adenomatous Polyposis Coli 
In mid- 1991 the gene responsible for familial ade- 
nomatous polyposis coli (APC) was identified in Dr. 
White's laboratory, after a molecular search of the 
region of human chromosome 5q2 1 that had been 
identified by linkage studies in families exhibiting 
this autosomal dominant disease. Nothing was 
known about the gene before it was found, but the 
putative physiological role of APC as a tumor sup- 
pressor had made it a target of interest in a number 
of laboratories. Affected members of APC families 
are predisposed to colon cancer because adenoma- 
tous colonic polyps, precursors of both sporadic 
and inherited carcinomas, usually become numer- 
ous in early adulthood. Although APC is a rare dis- 
ease, an understanding of the causative gene could 
shed light on the mechanisms leading to common, 
presumably nonfamilial colon cancers as well. 
Identification of new mutations. Several ap- 
proaches to characterizing APC and its mutant forms 
are under way in Dr. White's laboratory. Dr. Joanna 
Groden continues to identify mutations in the con- 
stitutional DNA of APC patients, by single-strand 
conformation polymorphism (SSCP) analysis and by 
DNA sequencing. Nearly all of the mutations in APC 
found to date, here or elsewhere, have consisted of 
base-pair changes leading to stop codons or of small 
deletions leading to shifts in the reading frame. 
Many of them are unique to a single kindred. 
Few mutations have been detected in the small 
284 
