Duronio R J, Bonnette P C, O'Farrell P H
Department of Biology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill 27599, USA.
Mol Cell Biol. 1998 Jan;18(1):141-51. doi: 10.1128/MCB.18.1.141.
Activation of heterodimeric E2F-DP transcription factors can drive the G1-S transition. Mutation of the Drosophila melanogaster dE2F gene eliminates transcriptional activation of several replication factors at the G1-S transition and compromises DNA replication. Here we describe a mutation in the Drosophila dDP gene. As expected for a defect in the dE2F partner, this mutation blocks G1-S transcription of DmRNR2 and cyclin E as previously described for mutations of dE2F. Mutation of dDP also causes an incomplete block of DNA replication. When S phase is compromised by reducing the activity of dE2F-dDP by either a dE2F or dDP mutation, the first phenotype detected is a reduction in the intensity of BrdU incorporation and a prolongation of the labeling. Notably, in many cells, there was no detected delay in entry into this compromised S phase. In contrast, when cyclin E function was reduced by a hypomorphic allele combination, BrdU incorporation was robust but the timing of S-phase entry was delayed. We suggest that dE2F-dDP contributes to the expression of two classes of gene products: replication factors, whose abundance has a graded effect on replication, and cyclin E, which triggers an all-or-nothing transition from G1 to S phase.
异二聚体E2F-DP转录因子的激活可驱动G1期向S期的转变。果蝇dE2F基因的突变消除了G1期向S期转变时几种复制因子的转录激活，并损害了DNA复制。在此，我们描述了果蝇dDP基因中的一个突变。正如dE2F伙伴缺陷所预期的那样，该突变如先前dE2F突变所描述的那样，阻断了DmRNR2和细胞周期蛋白E的G1期向S期转录。dDP的突变也导致DNA复制的不完全阻断。当通过dE2F或dDP突变降低dE2F-dDP的活性而损害S期时，检测到的第一个表型是BrdU掺入强度的降低和标记时间的延长。值得注意的是，在许多细胞中，未检测到进入这种受损S期的延迟。相反，当通过次等位基因突变组合降低细胞周期蛋白E的功能时，BrdU掺入强烈，但S期进入的时间延迟。我们认为，dE2F-dDP有助于两类基因产物的表达：复制因子，其丰度对复制有分级影响；细胞周期蛋白E，其触发从G1期到S期的全或无转变。
