DNA Stretching Mystery and Chaperone Enzyme Provides new Target for Cancer Treatments

DNA STRETCHING MYSTERY AND

CHAPERONE ENZYME PROVIDES NEW

TARGET FOR CANCER

TREATMENTS 

María Fernanda Molina

Medicine Student

FOLDING

FOLDING

INTRODUCTION

JILA work shows that DNA's backbone does not need to have a small gap,

often called a nick, or sport loose ends for the dramatic extension to occur at

65 pN.

Scientist discovered how a "chaperone" enzyme plays a key role in cells' ability to tolerate the DNA damage that leads to cancer and other diseases

STRETCHING THE TRUTH: BIOPHYSICISTS HELP UNRAVEL

DNA STRETCHING MYSTERYSCIENCE DAILY (JAN. 21, 2011)

STRETCHING THE TRUTH: BIOPHYSICISTS HELP UNRAVEL

DNA STRETCHING MYSTERY

The leading theory is that overstretching introduces so much energy that the DNA melts, with a single strand peeling off from nicks in the backbone or free ends. This model assumes that nicks or ends are essential.

STRETCHING THE TRUTH: BIOPHYSICISTS HELP UNRAVEL DNA

STRETCHING MYSTERY

The JILA team's key advance was a clever geometry that binds a looped end of DNA to a micro-sized bead, while the other end of the DNA has both strands stapled to a surface. Lasers apply force to the bead and measure its position.

STRETCHING THE TRUTH: BIOPHYSICISTS HELP UNRAVEL DNA

STRETCHING MYSTERY

The DNA has freedom to rotate but, crucially, no loose ends. The researchers compared one piece of DNA without nicks or free ends to another piece of DNA they had nicked.

STRETCHING THE TRUTH: BIOPHYSICISTS HELP UNRAVEL DNA

STRETCHING MYSTERY

They found that both molecules overstretched at essentially the same force, indicating the same mechanism is at work in both cases.

OBSERVATION

I think we should continue the investigation about DNA stretching just to know how drugs and

other substances bind to DNA and know how to

treat if they causes damage to it.

CHAPERONE ENZYME PROVIDES NEW TARGET FOR CANCER

TREATMENTSSCIENCE DAILY (JAN. 20, 2011) 

CHAPERONE ENZYME PROVIDES NEW TARGET FOR CANCER TREATMENTS

The enzyme, known as Rad18,

detects a protein

called DNA polymerase eta (Pol eta) and

accompanies it to the

sites of sunlight-induced

DNA damage, enabling accurate repair.

When Pol eta is not present,

alternative error-prone

polymerases take its place

-- a process

that leads to DNA

mutations often

found in cancer cells.

CHAPERONE ENZYME PROVIDES NEW TARGET FOR CANCER TREATMENTS

In one known example, faulty DNA repair due to Pol eta- deficiency is responsible for the genetic disease xeroderma pigmentosum-variant, which makes patients extremely susceptible to skin cancers caused by exposure to sunlight.

CHAPERONE ENZYME PROVIDES NEW TARGET FOR CANCER TREATMENTS

"We found that the mechanism that promotes the 'chaperone' enzyme to recruit Pol eta to sites of DNA damage is managed by another signaling protein termed 'Cdc7' which we know is essential to normal regulation of the cellular lifecycle," said lead author Cyrus Vaziri.

CHAPERONE ENZYME PROVIDES NEW TARGET FOR CANCER

TREATMENTSThus cells employ Cdc7 to ensure accurate DNA repair during the stage of their lifecycle that is most vulnerable to cancer-causing mutations. According to Vaziri, the dual role that Cdc7 plays in the cell lifecycle and DNA repair offers a promising target for potential cancer therapies.

OBSERVATIONwe should continu

e  research on this

topic to reduce

mortality from canc

er  because simple

activities as

smoking and

being exposed to

sun creates mutations t

hat lead into cancer.

MEDICAL UTILITY

MEDICAL UTILITY

DNA manages to suddenly extend to almost twice its normal length. The new test structure should support research on DNA elasticity as a standard for tiny forces and help refine studies of how drugs and other substances bind to DNA.

drug

MEDICAL UTILITY

UNC scientists found the mechanism that

promotes the 'chaperone' enzyme to recruit DNA polymerase eta (Pol eta) to sites of DNA damage that it´s managed by another

signaling protein termed 'Cdc7' which is known as essential to normal regulation of the cellular lifecycle.

The dua

l role that

Cdc7

plays in

the cell lifecycle

and DNA

repair offers a

promising target for potential cancer therapies. The cancer cells

have

high

levels of

Cdc7

activity and can evade some DNA-damaging

therapies

BIBLIOGRAPHY

 http://www.sciencedaily.com/releases/2011/01/110120111326.htm

 http://www.sciencedaily.com/releases/2011/01/110118143220.htm