Carolina Madrid Cardona

Medicine student

Universidad pontificia bolivariana

Medellín

Febrero 13, 2012

1 DNA molecule replication process

semiconservative

DNA damge:•Metabolic accident

•Radiation•Chemical exposition

•Replication•Transcription•translation

Mutationpossible eliminati

on of cell line

Damage response

•Damage elimination•Activation of control points•continuity restora-tion double helix•transcriptional response•Apptosis

“A constellation of defective proteins suspected in causing a malfunction in the body's ability to repair its own DNA could be the link scientists need to prove a new class of drugs will be effective in treating a broad range of ovarian cancer patients, an Oregon Health & Science University Knight Cancer Institute study found” ScienceDaily (Jan. 13, 2012) 

Several forms of cancerDepend on PARP Growth

targeting these enzymes when they go haywire is a potentially effective way to treat ovarian cancer

•Currently PARP inhibitors are being tested with patients who have two types of malfunctioning proteins, BRCA1 or BRCA2

Only about 10 to 15 percent of women with ovarian cancer have BRCA 1 or BRCA 2 mutations.

Pejovic's study

186 patients with nonhereditary

41 % who had an early recurrence of the disease also had abnormal levels of the other proteins tracked.

19.5% of patients who hadn't yet had a recurrence of the disease in three years had abnormal levels of these proteins.

there is evidence that these proteins influence a patient's ability to respond to drugs and their survival rates after treatment

"If we are able to identify the proteins that differentiate these patients at risk for early recurrence, this would open up a new direction in ovarian cancer treatment" Pejovic

the study focused on proteins that are supposed to assist cells in repairing harmful breaks in DNA strands, a process called homologous recombination (HR)

in order to find a cure for ovarian cancer, scientist should focus research into finding better ways to understand DNA reparations mechanism and indentify how they are related to a specific disease and the possible modifications that could be done into them for some treatment; in this case, they should pay special attention to broken double helix repair by recombination and the role of proteins in cancer cell metabolism

In the chemistry of the living world, a pair of nucleic acids -- DNA and RNA -- reign supreme. As carrier molecules of the genetic code, they provide all organisms with a mechanism for faithfully reproducing themselves as well as generating the myriad proteins vital to living systems. Science Daily (Jan. 9, 2012) 

Chaput and other researchers

Study to identify molecules that may have acted as genetic precursors to RNA and DNA

TNA.

contender

A nucleic acid similar in form to both DNA and RNA,

differs in the sugar component of its structure, using threose rather than deoxyribose (as in DNA) or ribose (as in RNA) to compose its backbone.

Could a simpler, self-replicating molecule have existed as a precursor to RNA, perhaps providing genetic material for earth's earliest organisms?

TNA uses tetrose sugars that are simpler than the pentose sugars found in both DNA and RNA

could assemble more easily in a prebiotic world, from two identical two-carbon fragments.

a single strand of TNA can bind with both DNA and RNA by Watson-Crick base pairing

.

molecular evolution to explore TNA's potential as a genetic biomolecule

Extending this technique to TNA requires polymerase enzymes that are capable of translating a library of random DNA sequences into TNA

TNA nucleotides could attach by complementary base pairing to a random sequence of DNA, forming a hybrid DNA-TNA strand by A DNA polymerase enzyme

high yield of DNA-TNA hybrid strands was produced when guanine was excluded

issues concerning the prebiotic synthesis of ribose sugars and the non-enzymatic replication of RNA may provide circumstantial evidence of an earlier genetic system more readily produced under primitive earth conditions

capable of storing information, undergoing selection processes and folding into tertiary structures that can perform complex functions

the most important finding to come from this work is that TNA can fold into complex shapes that can bind to a desired target with high affinity and specificity.

this discovery could be extremely important to fill up the spaces left between evolution process and could led to all the unanswered questions of the origin of life itself and the impact of it in the present. It could also be a base to start research some pathologies that could have started a long time ago in other organism and see how they fought it and then apply this responses into human body or other in order to create a better life time

Life has been going on during lots and lots of time. It started ever since prokaryots and evolved to eukaryots . There one of the most important molecules took place, RNA. And then the appearance of DNA.

the eukaryot was formed when the chloroplast and a mitochondria where endocytosed by a bacteria. Even from this far ago a disease placed on a mitochindria could have it’s explanation. For example, diabetes milletus, leigh sindrome and others are causesd by alterations in the protiens of mitochondria. This as indication of the relevance of understanding where we come from, to go from there to the future.

If we take under consideration this history we could realize that the base of a lot of pathologies have its origin in gentics and it may be a good approach to generate a treatment.

One example for it, it’s the genomic therapy. This involves the insertion of functional copies absent in the genome of an individual. It can be used for diseases like beta talasemias, Wiskott-Aldrich sindrome(WAS) cancer, etc.

It is also important to check the role of proteins in the replication of DNA and the way they keep the cell genoma. For example, BRCA1 and BBRCA2 A class of checkpoint mediator proteins,p53 that induces apoptosis if the DNA is wrong, and others.

These proteins mightbe helpful in front of virus diseases, that alter de cell DNA for life and a reverse transcriptase is needed to trate it.

Other proteins are the ones foud reicently, PPAR, if they are bloqued it may reduce proliferation of cancer cells. Tapping into the potential of PARP inhibitors could change the dynamics of ovarian cancer treatment and prevent over 14,000 deaths occur each year from the disease.

the role of some proteins in cancers where there is no family history of the disease is not well understood;however, there is evidence that these proteins influence a patient's ability to respond to drugs and their survival rates after treatment.

• MARTINEZ S,lina Maria. Biologia Molecular.5 ed Medellin: UPB. Fac medicina

• Faulty Proteins May Prove Significant in Identifying New Treatments for Ovarian Cancer. Science Daily (January 13, 2012)

• Simpler Times: Did an Earlier Genetic Molecule Predate DNA and RNA? Science Daily (January 18, 2012)