Featured Research

from universities, journals, and other organizations

Pathway to bypass DNA lesions in replication process is experimentally shown

Date:
November 30, 2012
Source:
Universidad de Barcelona
Summary:
DNA lesions are really common —- about one million individual molecular lesions per cell per day -— because its long strands usually have one missing base or are damaged. These lesions can stall the DNA replication process, what can lead to the cell death. To avoid it, there are several pathways to bypass lesions in order to continue with the process of DNA replication. One of these processes has been entirely reproduced in vitro using some techniques of manipulation of single-molecules.

The protein UvsW, together with the coordinated action of the polymerase, drives the system to its departure point, once “jumped” the lesion.
Credit: Image courtesy of Universidad de Barcelona

DNA lesions are really common -- about one million individual molecular lesions per cell per day -- because its long strands usually have one missing base or are damaged. These lesions can stall the DNA replication process, what can lead to the cell death. To avoid it, there are several pathways to bypass lesions in order to continue with the process of DNA replication. One of these processes has been entirely reproduced in vitro using some techniques of manipulation of single-molecules in a study published November 30 in Science, led by the researcher of the University of Barcelona Maria Mañosas.

Related Articles


"This pathway was proposed in the seventies and now we have been able to prove it on a bacteriophage through the manipulation of single-molecules that, oppositely to the traditional biochemical techniques that work with a great number of molecules, allows to study how a protein works on a molecule in real time," explains Mañosas, professor at the Department of Fundamental Physics of the UB, affiliated with the campus of International excellence, BKC.

To study a single-molecule, we used magnetic tweezers, a technique which consists on tethering a DNA hairpin between a glass surface and a magnetic bead. A magnetic system generates a magnetic field which allows manipulating the beads and generates magnetic forces. This system can be used in order to measure the extension changes of DNA strands through the screening of the magnetic beads. According to Mañosas, "proteins' activity over DNA can be inferred from the changes in the extension of the molecule. The changes are due to the proteins' work."

The template switching strategy

In the DNA replication process, the two strands who act as a template to synthesise a complementary strand are separated, and the new complementary strand joins each of the initial strands in order to obtain two identical copies of the original DNA molecule. In this process take part the polymerases, a family of enzymes that carry out all forms of DNA replication. When in any of the two derived strands there is a lesion, especially in the leading strand, the polymerase stops synthetizing the bases, so the replication process is stalled. "To stall this process can entail some problems in cellular growth," explains Mañosas. "When the replication mechanism (replisome) is disassembled, the bypass process analysed in this study starts," points out the author, member of the Biomedical Research Networking center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) and researcher at the University of Paris.

The studied process begins with the action of a helicase protein (UvsW) which promotes the binding of DNA strands, a phenomenon named DNA hybridization. This protein is also able to build an intermediate structure (Holliday junction) taking as a model the not damaged replicated strand and, together with the action of polymerase, drive the system to its departure point, once "jumped" the lesion, and then restart the DNA replication process. "Therefore, the information lost when one strand is damaged can be recovered from the other intact strand which acts as a backup; this process is named "the template switching strategy." In the study, we have also observed the regulation mechanisms of this pathway, as well as the rate of annealing of helicase UvsW, 1500 bases per second, one the largest known," concludes Mañosas.

DNA repair is essential in a great number of diseases. A deeper knowledge of these phenomena will enable us to act over some proteins which have similar functions in humans. Mañosas is working on this direction; she is carrying out a study on a human protein named HARP in order to know how it works, because it is known that it has a really important role in the genome conservation and its dysfunction is related to some types of cancer.


Story Source:

The above story is based on materials provided by Universidad de Barcelona. Note: Materials may be edited for content and length.


Journal Reference:

  1. M. Manosas, S. K. Perumal, V. Croquette, S. J. Benkovic. Direct Observation of Stalled Fork Restart via Fork Regression in the T4 Replication System. Science, 2012; 338 (6111): 1217 DOI: 10.1126/science.1225437

Cite This Page:

Universidad de Barcelona. "Pathway to bypass DNA lesions in replication process is experimentally shown." ScienceDaily. ScienceDaily, 30 November 2012. <www.sciencedaily.com/releases/2012/11/121130095027.htm>.
Universidad de Barcelona. (2012, November 30). Pathway to bypass DNA lesions in replication process is experimentally shown. ScienceDaily. Retrieved November 26, 2014 from www.sciencedaily.com/releases/2012/11/121130095027.htm
Universidad de Barcelona. "Pathway to bypass DNA lesions in replication process is experimentally shown." ScienceDaily. www.sciencedaily.com/releases/2012/11/121130095027.htm (accessed November 26, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Wednesday, November 26, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Pet Dogs to Be Used in Anti-Ageing Trial

Pet Dogs to Be Used in Anti-Ageing Trial

Reuters - Innovations Video Online (Nov. 26, 2014) — Researchers in the United States are preparing to discover whether a drug commonly used in human organ transplants can extend the lifespan and health quality of pet dogs. Video provided by Reuters
Powered by NewsLook.com
Today's Prostheses Are More Capable Than Ever

Today's Prostheses Are More Capable Than Ever

Newsy (Nov. 26, 2014) — Advances in prosthetics are making replacement body parts stronger and more lifelike than they’ve ever been. Video provided by Newsy
Powered by NewsLook.com
From Popcorn To Vending Snacks: FDA Ups Calorie Count Rules

From Popcorn To Vending Snacks: FDA Ups Calorie Count Rules

Newsy (Nov. 25, 2014) — The US FDA is announcing new calorie rules on Tuesday that will require everywhere from theaters to vending machines to include calorie counts. Video provided by Newsy
Powered by NewsLook.com
Daily Serving Of Yogurt Could Reduce Risk Of Type 2 Diabetes

Daily Serving Of Yogurt Could Reduce Risk Of Type 2 Diabetes

Newsy (Nov. 25, 2014) — Need another reason to eat yogurt every day? Researchers now say it could reduce a person's risk of developing type 2 diabetes. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins