Identification of new molecular mechanism indicates new ways to block uncontrolled cell division&

Study reveals intricate mechanisms involved in enzyme that governs DNA duplication

 

Julián Carvajal FernándezMolecular BiologyThird semester – 2014-02Teacher: Lina Maria Martinez SanchezUniversidad Pontificia Bolivariana

INTRODUCTION

Every human cell has DNA (Deoxyribonucleic acid). DNA is the genetic material that contains all information needed to create other cells and be part of an organism.

All natural aspects of our bodies are defined by DNA and it´s function can explain lots of anormalities we suffer when we get sick.

There lies the importance of the fact on knowing it´s behavior.

-ORI-MCM2-7 Helicase-RNA Polymerase -DNA Polymerase

-Primase-Topoisomerase

-DNA ligase-SSDBP

-RNAse H

• DNA replication is a molecular process that happens when genetic information is duplicated at division time.

• This event requires a serie of steps perfomed by some proteins:

Study reveals intricate mechanisms involved in enzyme that governs DNA duplication

 

Replication mechanism

DNA is unrolled by Topoisomerase

MCM2-7 helicase recognize ORI and open the strands

SSDBP mantain separate the

strands

Primase synthesizes the

primer

Primers are eliminated by

RNAse H, creating okasaki fragments

Resulting holes are filled by d-

Polymerase and DNA ligase binds the

fragments

The copy get started

Topoisomerase release it´s unroll

and replication finish

This study was focused on the MCM2-7 helicase (hexamer).

Until now, the way how MCM2-7 helicase separates the two strands was unknown.Previous theories established that MCM2-7 helicase was in an open ring conformation.

Speck`s group argued that this would be an undoubtedly lead to poorly regulated DNA replication with no specificity and control.

So they discovered with advanced technology and an electron microscope that these theories were wrong. They discovered that MCM2-7 helicase exists in a closed ring conformation.

Next step was to pinpoint where within the six subunits, the helicase open to encompass the DNA.

They found that if they blocked one specific interface, between MCM2 and MCM5, DNA could not enter.

"Our work is aimed at understanding the molecular mechanism of

DNA replication at a fundamental level. Yet our findings could also have important

implications, possibly pointing to new ways to fight cancer, because DNA

duplication is a prime target to inhibit cancer cell growth," says Christian.

OPINION

All type of discoveries that helps and lead new methods on facing cancer are vital. Now there is whole new field to keep working on it`s treatment. So, every new knowledge about the behavior of DNA is very important.

Identification of new molecular mechanism indicates new ways

to block uncontrolled cell division

• An especial proteín, protagonist in DNA replicaction was studied by Dr Christian Speck`s group, Helicase MCM2-7.

• It`s function, separate the two strands of DNA in DNA replication was already known. But the poor information about it`s mechanism and structure, were not good established yet.

Trying to find the answer about the Helicase MCM2-7 function and structure, Speck`s team developed a sophisticated system using synthetic, chemical and structural biology approaches.

They revealed using an electron microscope that the helicase is actually an hexamer with a closed ring conformation, contrary to initial theories who established that Helicase MCM2-7 was an hexamer with an open ring conformation.

This finding is consistent with the specificity that this protein must have.

To determinate where within the six subunits, the helicase opens to encompass the DNA, the team generated linkages that blocked ring opening at various positions.

They found that if they blocked one specific interface, between MCM2 and MCM5, DNA could not enter. A small molecule called rapamycin brings the linkages together; such a molecular switch can be used to control DNA entry to the MCM ring and subsequent DNA replication.

“Both in the context of our in vitro and in vivo experiments, we showed that opening of the MCM2/MCM5 interface is essential for helicase loading onto DNA” explains Christian.

"The field has known for a while that DNA can pass into the MCM2-7 ring, but has never been sure which MCM subunits are used for regulated helicase loading. By designing an elegant experiment, the Speck laboratory has now shown once and for all that the MCM2-5 is the only DNA entry point," says collaborator Huilin Li at BNL.

In a successful collaboration that harnesses the electron microscopy expertise at BNL with the chemical biology and genetic expertise at the MRC Clinical Sciences Centre, the study addresses key questions detailing the processes involved in DNA replication.

OPINION

It is important to consider the relevance of advanced technology today. Based on a good technological support and a solid group of people, major findings can occur, as we can see here… A new line to invest how to confront cancer.

DNA controls all cellular processes, and that is a fact that determinates our health.

That is why today, there are many efforts to understand it`s functioning.

MEDICAL UTILITY

MEDICAL UTILITY

Cancer occurs when the growth of our cells is out of control and cells divide too fast, or in fact, when they forget to die.

That is why, knowing the operation mechanism of DNA we can search solutions to this disease.

MEDICAL UTILITY

If we certainly know about all factors that acts on DNA replicaction, we can search ways to stop it when it`s necesary, stoping cell growth on situations like cancer.

MEDICAL UTILITY

The most important think about this topic is never give up on fighting cancer. Protagonist of this news are a perfect example of it. With this finding they open lights to other researchers to keep trying, and they showed that there is a lot to do against this disease.

• ¨Identification of a new molecular mechanism indicates new ways to block unctrolled cell division”

http://www.news-medical.net/news/20140801/Identification-of-new-molecular-mechanism-indicates-new-ways-to-block-uncontrolled-cell-division.aspx (accesed 05/08/2014)

• ¨ Study reveals intricate mechanisms involved in enzyme that governs DNA duplication.”

http://www.news-medical.net/news/20140804/Study-reveals-intricate-mechanisms-involved-in-enzyme-that-governs-DNA-duplication.aspx(accesed 05/08/2014)

• MARTINEZ SÁNCHEZ, Lina María. Biología molecular. 7. ed. Medellin: UPB Fac. de Medicina, 2012. 78-83p.

• http://www.nlm.nih.gov/medlineplus/spanish/ency/article/001289.htm (accesed 09/08/2014)

BIBLIOGRAPHY

“Limits are for those who do not know the power of their minds”

Julián Carvajal Fernández