A DNA repair pathway

[Zack Clayton <zclayton@YAHOO.COM>]

Found this on Science Daily News, and thought it would be of some

interest to the group.



Zack Clayton

HP3

Columbus, Ohio



Source:  

	

University Of Southern California

Date:  2004-12-14

	

USC-led Team Of Scientists Recreates DNA-mending Pathway In Test-tube



Los Angeles (Dec. 2, 2004) -- One of five known DNA-repair mechanisms

in cells has been completely analyzed and reconstituted in a test tube

by an international collaboration of researchers led by scientists from

the Keck School of Medicine of the University of Southern California.

The team is the first ever to reconstitute this pathway, known as the

nonhomologous end joining pathway, or NHEJ, and NHEJ is only the third

repair pathway to be reconstituted in the laboratory.



>From left, Michael Lieber, Myron Goodman, and Chih-Lin Hsieh. (Photo

Credit: Jon Nalick / Courtesy of University Of Southern California)

	

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The findings were published in the December 3, 2004 issue of Molecular

Cell.



Understanding how DNA repair works is critical to understanding the

development of cancer, which often occurs when DNA is not properly

repaired.



In addition, notes Michael Lieber, M.D., Ph.D., the Rita and Edward

Polusky Chair in Basic Cancer Research at the Keck School who heads up

the molecular genetics program at the USC/Norris Comprehensive Cancer

Center and was principal investigator on this study, the ability to

reconstitute the pathway has important practical implications.



"Now we can really test for drugs that will affect the pathway," he

said. "For instance, one of the things this pathway is particularly

good at is repairing radiation damage. When people get radiation

treatment, both the normal and the tumor cells will use this pathway to

resist the radiation. If we could inhibit the pathway regionally in or

around the tumor, we could really make radiation dramatically more

effective."



In order for the team to reconstitute the NHEJ pathway, which is found

in all cells that are evolutionarily 'above' yeast, they first had to

purify all the proteins used to rejoin the double strands of DNA once

they've suffered damage and are severed from one another. As it turned

out, two of the seven proteins come from a class of polymerases that

were discovered in 1999 by Myron Goodman, Ph.D., professor of molecular

biology at the USC College of Letters, Arts and Sciences, who became an

essential part of this research team.



"Before this, no one knew what this class was good for," Lieber

explains. "This is really the first solid indication of what two of

these polymerases might do."



Knowledge of the details of the NHEJ pathway extends beyond its

connections to cancer and radiation treatment, Lieber notes.



"This pathway gets used not just for accidental damage, oxidative

damage and radiation damage to DNA, but is also used in the immune

system," he explains. "So the immune system would function less well

without it."



###



The work featured in Molecular Cell was supported by the National

Institutes of Health.



Yunmei Ma, Haihui Lu, Brigette Tippin, Myron F. Goodman, Noriko

Shimazaki, Osamu Koiwai, Chih-Lin Hsieh, Klaus Schwarz, Michael R.

Lieber, "A Biochemically Defined System for Mammalian Nonhomologous DNA

End Joining." Molecular Cell, Volume 16, Number 5, December 3, 2004.







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