7.06 Problem Set Four, 2006
Explain the molecular mechanism behind each of the following events that occur during the
cell cycle, making sure to discuss specific proteins that are involved in making each event
During G1 phase, cells pass through the Restriction Point if growth factors are present in the
Growth factors are sensed by RTKs, which then become activated and thereby activate, in
linear order, GRB2, Sos, Ras, Raf, MEK, and finally MAP kinase.
MAP kinase therefore
dimerizes and enters the nucleus, where it regulates transcription factors that control genes
that are necessary for the progression of cells through the Restriction Point (i.e. genes
necessary to promote the occurrence of events in the cell cycle).
During S phase, origins of replication fire.
When we say that origins “fire,” what we mean is the DNA replication initiates from that
This occurs because the origin replication complex ORC recognizes and binds to
origins of replication.
ORC acts as a landing pad for Cdc6 and Cdt1.
These two proteins
lead to the recruitment of MCM proteins, which allow for the melting of the DNA at
Once the DNA is melted into single-stranded DNA, a replication bubble is formed,
to which DNA polymerase is recruited.
During S phase, each origin of replication never fires more than once.
The “firing” of origins that is described above triggers disassembly of the pre-replicative
complex (the proteins bound at the origin named above).
A functional pre-RC cannot be
formed at the origin again until cells have progressed through the cell cycle to the next G1
This is because Cdt1, an essential part of the pre-RC, is degraded after origins fire,
and is not resynthesized until cells have proceeded through M phase.
During prophase of mitosis, chromosomes become condensed.
Once cells enter S phase, the cells start to accumulate mitotic cyclins (B-type cyclins).
These cyclins associate with CDKs, and upon activation of the mitotic cyclin/CDK
compexes at the G2/M boundary, these complexes phosphorylate condensin complexes.
Condensins are proteins that organize and compact chromatin into tightly wound
structures. Phosphorylated condensins associate with chromosomes and condense
During prophase of mitosis (in many cell types, but not in yeast), the nuclear membrane