Affiliation:
1. Massachusetts General Hospital Cancer Center, Charlestown, Massachusetts
2. Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois
Abstract
ABSTRACT
To gain insight into the essential functions of E2F, we have examined the phenotypes caused by complete inactivation of E2F and DP family members in
Drosophila
. Our results show that dDP requires dE2F1 and dE2F2 for DNA-binding activity in vitro and in vivo. In tissue culture cells and in mutant animals, the levels of dE2F and dDP proteins are strongly interdependent. In the absence of dDP, the levels of dE2F1 and dE2F2 decline dramatically, and vice versa. Accordingly, the cell cycle and transcriptional phenotypes caused by targeting dDP mimic the effects of targeting both dE2F1 and dE2F2 and are indistinguishable from the effects of inactivating all three proteins. Although
trans-
heterozygous
dDP
mutant animals develop to late pupal stages, the analysis of somatic mutant clones shows that
dDP
mutant cells are at a severe proliferative disadvantage when compared directly with wild-type neighbors. Strikingly, the timing of S-phase entry or exit is not delayed in
dDP
mutant clones, nor is the accumulation of cyclin A or cyclin B. However, the maximal level of bromodeoxyuridine incorporation is reduced in
dDP
mutant clones, and RNA interference experiments show that dDP-depleted cells are prone to stall in S phase. In addition,
dDP
mutant clones contain reduced numbers of mitotic cells, indicating that
dDP
mutant cells have a defect in G
2
/M-phase progression. Thus,
dDP
is not essential for developmental control of the G
1
-to-S transition, but it is required for normal cell proliferation, for optimal DNA synthesis, and for efficient G
2
/M progression.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
Cited by
39 articles.
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