Fundamentals of Cell Biology

Chapter 7: The Nucleus and DNA

Replication

Chapter Summary: The Big Picture (1)

Chapter foci:
Examine the anatomy of the nucleus
Introduction to the protein complexes necessary for
building, replicating, and maintaining the structure
of DNA
Discussion of mitosis and the importance of the
cytoskeleton in regulating mitosis

Chapter Summary: The Big Picture (2)

Section topics:
The nucleus contains and protects most of a
eukaryotic cells DNA
DNA replication is a complex, tightly-regulated
process
Mitosis separates replicated chromosomes

The nucleus contains and protects most of

a eukaryotic cells DNA
Key Concepts:
The nucleus is a highly-specialized organelle
committed primarily to protecting, copying, and
transcribing DNA.
The interior of the nucleus is highly
compartmentalized.
DNA copying, plus transcribing and splicing of RNA,
are accomplished by large, highly-specialized
molecular complexes.

The nuclear envelope is a double

membrane structure
the nuclear envelope encloses the
nucleoplasm
outer membrane of the nuclear
envelope is continuous with the ER

Nuclear pore complexes regulate

molecular traffic into and out of the nucleus
layers of rings stacked
on top of one another
that span the nuclear
membranes, linked to
filamentous protein
fibrils to form a basket
structure
structure undergoes
complex conformational
changes when it
transports material into
and out of the nucleus

The interior of the nucleus is highly

organized and contains subcompartments
nucleolus contains DNA that
encodes ribosomal RNAs
nucleoli are sites of high
transcriptional activity for
rRNA genes

The nuclear matrix helps to organize

chromosomes
chromosomes are
compartmentalized into
regions called chromosome
territories
nuclear matrix helps control
the shape of chromosomes
and regulate
heterochromatin and
euchromatin

DNA replication occurs at sites called

replication factories
DNA replication factories form large complexes in the
nucleus devoted to copying DNA with 100%
accuracy and no breaks
Replisome is the smallest functional unit in the
factories and are responsible for copying one
segment of DNA

RNA polymerase complexes and

spliceosomes are distinct structures within
the nucleus
RNA polymerase complexes are responsible for
transcribing the DNA sequence in genes into
mRNA, rRNA, tRNA, and other RNAs
Spliceosomes are responsible for splicing the
newly synthesized RNAs into their mature form

DNA replication is a complex, tightlyregulated process

Key Concepts (1):
DNA replication in all organisms is performed by a
small number of highly-conserved proteins.
Both prokaryotes and eukaryotes express different
forms of DNA polymerase, the enzyme responsible
for synthesizing DNA.
DNA replication begins at specific sites called origins
of replication.
During replication, double-stranded DNA is unwound
and dissociated into single strands that serve as
templates for synthesis of complementary DNA
strands.

DNA replication is a complex, tightlyregulated process

Key Concepts (2):
DNA synthesis occurs only in the 5-to-3 direction.
DNA polymerases must bind a double-stranded portion of
a DNA molecule to begin synthesis. Most often, the double
strand consists of the template DNA strand and a short,
complementary RNA primer.
DNA ligase connects individual pieces of newly
synthesized DNA to form a complete strand.
The enzyme telomerase adds extra DNA to the ends of
chromosomes to protect them from degradation.

DNA polymerases are enzymes that

replicate DNA

DNA polymerases
DNA polymerases add
deoxyribonucleotides to
the 3 end of DNA strand
DNA polymerases
proofread their work

DNA replication is semi-discontinuous

DNA replication begins
at sites on
chromosomes called
origins of replication
During replication,
specialized proteins
unwind and separate
the two strands to form
a replication fork

The replication complex

DNA replication is semi-discontinuous

DNA replication requires
an RNA primer
leading/lagging strand
Okazaki fragments
DNA ligases join
fragments of singlestranded DNA

Replication of DNA at the end of

chromosomes requires additional steps

Cells have two main DNA repair

mechanisms
Excision repair systems
Mismatch repair
Recombination repair

Mitosis Separates Replicated

Chromosomes
Key Concepts:
The function of mitosis is to safely separate
replicated chromosomes into two daughter cells.
Mitosis is divided into five phases, based largely on
morphological changes in the location and
arrangement of chromosomes.
The microtubule cytoskeleton, including microtubule
motor proteins, is essential for proper segregation of
chromosomes.
The actin cytoskeleton is required for the actual
division of one cell into two daughter cells following
mitosis.

Mitosis is divided into stages

1879 - Walther Flemming
described the motion of what
he saw under microscope
as threads (Greek, mitos)
moving in an actively
dividing cell

Prophase prepares the cell for division

Motors contribute to the formation of

the mature spindle in prophase
Dynein motor proteins
Kinesin-related motor proteins

Chromosomes attach to the mitotic

spindle during prometaphase
Kinetochores attach chromosomes to the mitotic
spindle

Arrival of the chromosomes at the

spindle equator signals the beginning
of metaphase
Metaphase plate = spindle equator

Separation of chromatids at the metaphase

plate occurs during anaphase
The onset of anaphase requires dissolving the
connections between sister chromatids
APC

Separation of chromatids at the metaphase

plate occurs during anaphase
Anaphase is subdivided into two phases:
anaphase A
anaphase B

Telophase - Cytokinesis
The structural rearrangements that occur in
prophase begin to reverse during telophase
Cytokinesis completes mitosis by partitioning the
cytoplasm to form two new daughter cells
Fragmentation of non-nuclear organelles
ensures their equal distribution in the daughter
cells