Major events during initiation and finishing of DNA

replication
Alberts et al: Mol Bio of the Cell

Cell Molecular Biology, N Dhami, Pokhara

University Nepal

Initiation of DNA replication: replicon model

DNA replication starts at a particular region
called replicator
REPLICATOR (Origin of replication) region is a
set of DNA sequences that direct the
initiation of replication
INITIATOR protein specifically recognizes a
DNA element in the replicator and activates
the initiation of replication

Follow: Watson et al; Molecular biology of the Gene

Cell Molecular Biology, N Dhami, Pokhara
University Nepal

Replicator sequences include Initiator binding sites

Initiator binding site

Synthesis site

unwinding site

Cell Molecular Biology, N Dhami, Pokhara

University Nepal

Initiator protein binds to

replicator sequences and
induces unwinding of
DNA double helix

Cell Molecular Biology, N Dhami, Pokhara

University Nepal

Initiation of DNA
replication in E. coli

Cell Molecular Biology, N Dhami, Pokhara

University Nepal

Initiation of DNA
replication in E. coli

Cell Molecular Biology, N Dhami, Pokhara

University Nepal

Initiation of DNA
replication in E. coli

Cell Molecular Biology, N Dhami, Pokhara

University Nepal

Eukaryotic DNA replication is much complex

DNA replication in eukaryotes and prokaryotes is
fundamentally similar however components
varies
Eukaryotic initiator is six protein complex known
as Origin recognition complex (ORC)
Enough origins must be activated to ensure that
each chromosome is fully replicated during each
S phase
Cdk and Ddk proteins inhibit activation of origins
until the next round of cell division
Cell Molecular Biology, N Dhami, Pokhara
University Nepal

Pre replicative complex

formation directs the
initiation of DNA
replication in eukaryotes
Cell division
cycle6 protein
Replication factor

Mini-chromosome
maintenance proteins

Cell Molecular Biology, N Dhami, Pokhara

University Nepal

Pre-RC formation and activation is

regulated by Cdk & Ddk proteins

Cell Molecular Biology, N Dhami, Pokhara

University Nepal

Cdks regulates pre-RC

formation and
activation

Cell Molecular Biology, N Dhami, Pokhara

University Nepal

Cdks determine DNA replication

once and only once in eukaryotes

Cell Molecular Biology, N Dhami, Pokhara

University Nepal

Finishing of DNA replication

Cell Molecular Biology, N Dhami, Pokhara

University Nepal

End replication problem

Cell Molecular Biology, N Dhami, Pokhara

University Nepal

Telomerase (a
ribonucleoprotein) has a
reverse transcriptase
activity

Cell Molecular Biology, N Dhami, Pokhara

University Nepal

Telomerase solves the end

replication problem

Cell Molecular Biology, N Dhami, Pokhara

University Nepal