1) Scientists have reconstituted the DNA "replication fork" for the first time, allowing them to study the complex process of DNA duplication. 2) Researchers discovered that an enzyme involved in metabolizing carbohydrates, pyruvate dehydrogenase complex (PDC), is present in the nucleus and can acetylate histones to regulate DNA replication and gene expression. 3) Understanding how DNA replicates and is regulated could help scientists develop treatments for diseases like cancer by controlling genetic and epigenetic processes involved in uncontrolled cell growth.

1. Sweet genesSweet genes: New way found by: New way found by
which metabolism is linked to thewhich metabolism is linked to the
regulation of DNAregulation of DNA
AND
DNA 'replication fork' reconstitutedDNA 'replication fork' reconstituted
for the first timefor the first time
Ana Cristina Toro Moreno
Medical Student
3rd Semester
Molecular Biology 2014-02
Universidad Pontificia Bolivariana
Teacher: Lina Maria Martínez Sánchez

4. INTRODUCTION
DNA or Deoxyribonucleic acid is the basis of our
genetic code, it contains all the genetic instructions
that control cell development and function. Every
cell of our body has DNA.
DNA divides , replicating itself, giving two daughter
strands, which contain exactly the same genectic
instructions as the mother DNA. Then it transcripts
into RNA and finally it traduces into proteins. This
process is known as the Central Dogma of the
genetic information.
The problem remains, in DNA replication. Scientists
keep an eye on it, because it is said that most of
diseases start in the replication fork, and studying
it, may help in the future understand the problems
that it can suffer, and help people that has cancer
and other diseases to get cure.

5. DNA ‘REPLICATION FORK’
RECONSTITUDED FOR THE FIRST
TIME
JULY 9, 2014– ROCKEFELLER UNIVERSITY
When a cell divides, it first needs
to make a copy of its DNA. It
replicates into two exact
daughter copies.
1Replication is a
semiconservative process (old
strand and a new strand).
2
Process that occurs in the S
phase of cell cycle
3

6. REPLICATION
Helped by DNA polymerases,
enzymes that catalyzes the union of
dNTP (deoxyribonucleotids 5’
trifosphates) to create the daughter
DNA strand.
In Eukaryotic cells
α  nucleus
δ  nucleus
ε  nucleus
γ  mitochondria
β  reparation
Components
• ORI: located in the middle of the fork
(bubble). Recognized by union proteins.
• Replication fork: place where replication
takes place (the bubble).
• Okazaki fragments: little pieces in
discontinuous strand.
• DNA ligase: responsable of the union of
okazaki fragments.
• Helicase: unwraping of the mother DNA,
breaks down hidrogen bridges between the
bases.
• Primase: catalyzes formation of primers.
• SSDBP: Helps the DNA stabilization in a sigle
strand.
• Topoisomerases: enzymes that split down
the DNA.
• RNAse H: Split down DNA primers.

7. • PACE 1:
-Recognizing ORI by
helicases.
-Formation of the
fork(bubble).
• PACE 2:
-Manteining the fork.
-SSDBP binds to the
nucleotids of the
strand .
• PACE 3:
- Synthesis of the
primer.
- RNAse H splits the
RNA primer
- Spaces filled by Pol δ,
and fragments are
binded by the DNA
• PACE 4:
-Replication iniciates.
• PACE 5:
-Topoisomerases relaxes DNA wrappings.
• PACE 6:
-Replacation process is finished.
Check out the
graphic

8. REPLICATION FORK
• Complex of numerous proteins, one of them called CMG,
which unwinds and separates DNA into two individual strands.
• The two strands of double-stranded DNA are complementary,
they fit together head to tail (the 5' end to the 3' end), so that
the head of one strand is attached to the tail of the other.
• This leads to a traffic problem, where the two daughter
strands are created at different paces, resulting in a leading
strand (Pol ε) and a lagging strand (Pol δ) are being
synthesized in opposite directions (5’-3’ 3’-5’
respectively).
• Pol ε, does not attach very well to the DNA on its own. It
requires the presence of the CMG to attach securely. Even in
an excess of Pol δ, CMG chose Pol ε. Pol δ, however, binds
very strongly to an accessory protein, the PCNA clamp, a ring
shaped protein that encircles DNA. Only when the PCNA
clamp is on the lagging strand does Pol δ strongly bind to
PCNA.

9. OPINION
I my opinion this discovery is a big step in medicine and
in science. Just being able to understand a little bit of
how our DNA works is greatful to everyone.
If every discovery is useful to fix processes, many
diseases could be cured, and many people would
improve their quality of life.

10. SWEET GENES: NEW WAY FOUND BY WHICH
METABOLISM IS LINKED TO THE REGULATION
OF DNA
JULY 3, 2014– UNIVERSITY OF ALBERTA FACULTY OF MEDICINE AND
DENTISTRY
Histones are proteins that prevents the
expression of genes and the replication of DNA,
which are required for cell growth and division,
acting as spools around which DNA winds, creating
nucleosomes.

11. Epigenetic regulation of DNA
Is the process by which an Acetyl CoA group is donated
to the Histones, so they become acetylated. This
acetylation relaxes the DNA, allowing for DNA
replication and gene expression.
It was known that the enzyme that catalyze this
process, Pyruvate Dehydrogenase Complex, resided
only within the mitochondria, but now we know they
discovered that it resided
in the nucleus too.

12. Histone Acetylation

13. PDC
Generates Acetyl CoA
Mitochondria
Nucleus
Uses carbohydrates from
our diet
Energy production
Histone Acetylation

14. In my opinion this finding could help scientists
and doctors understand how a disease works,
how fast it grow, and how can we treat it. This
is great because we are in the “era” where
everyone is getting sick, so they could save
many lives.

15. MEDICAL UTILITYMEDICAL UTILITY
Cells have DNA, they need it in order to divide and
grow. Humans are made of cells, DNA keeps
development and reproduction available for us.
If DNA get damaged, it would replicate that way, so
when cell divides, it would have a damaged copy of
DNA. This is how starts a disease.

16. MEDICAL UTILITYMEDICAL UTILITY
This findings would help understand diseases. For
example with the replication fork, it was
understood a little bit of how those enzymes do
their work, and discovering PDC in the nucleus,
can help us see a little more of how DNA get
damaged and replicates that way.
If doctors and scientists could stop that, or fix that, people wouldn’t get sick, or
maybe we can start getting cures for some diseases like cancer and heart
failure.
Its obviously we have genes that afects our genetics and determine our
physiologic and pathologic conditions, but this discoveries, even if they seem
small, they aren’t. If we could fix a disease just before it starts, it would be the
sensation.

17. MEDICAL UTILITYMEDICAL UTILITY
With PDC in the nucleus, cancer cells grow faster.
Scientists could create a drug that may regulate
histone acetylation in both mitochondria and nucleus,
or a drug that slows down the translocation of the PDC
from the mitochondria to the nucleus. This might give
time to the pacients and to the doctors to start an
effective treatment that would stop cancer and
metastasis.

18. MEDICAL UTILITYMEDICAL UTILITY
• This findings have many
medical uilities, but most of
all it gives us faith and
determination to keep
looking for the source of
every disease.
• If we get to control genetic
and DNA that are the basis
of everything, we can
control the world, because
is us against diseases.
• It would help industry of
nanotechnology.

19. BIBLIOGRAPHY
• MARTÍNEZ SÁNCHEZ, Lina María, Biología Molecular, Séptima edición,
Medellín, 2012, págs. 74-84.
• http://books.google.com.co/books?
id=bgQ_xyJYkigC&pg=PA50&dq=DNA&hl=es-
419&sa=X&ei=hUjeU9K1O_XfsASd7YCYCA&ved=0CE4Q6AEwBg#v=onepag
e&q=DNA&f=false (accesed August 1, 2014)
• DNA ‘replication fork’ reconstituded for the first time
http://www.sciencedaily.com/releases/2014/07/140709100106.htm
(accessed July 22, 2014)
• Sweet genes: new way found by which metabolism is linked to the
regulation of DNA
http://www.sciencedaily.com/releases/2014/07/140703151821.htm
(accessed July 20, 2014)
• http://books.google.com.co/books?
id=sDQYRWEhVroC&pg=PA82&dq=histonas&hl=es-
419&sa=X&ei=UEneU9LrCu-
_sQSis4LIDA&ved=0CCEQ6AEwAQ#v=onepage&q=histonas&f=false
(accesed July 30, 2014)