Protein helps fix damaged DNA in yeast

July 30, 2010 By Krishna Ramanujan
To replicate the genome, the replication machinery must travel the full extent of the genomic DNA. But the machinery often stalls and is damaged by encountering DNA lesions or replication blocks along the way. Smolka and colleagues discovered how the Mec1 protein mediates the repair and restart of the replication machinery, so cells can complete DNA replication.

(PhysOrg.com) -- Like a scout that runs ahead to spot signs of damage or danger, a protein in yeast safeguards the yeast cells' genome during replication -- a process vulnerable to errors when DNA is copied -- according to new Cornell research.

Researchers from Weill Institute for Cell and Molecular Biology have discovered how a called Mec1 plays the role of "guardian of the genome," explained Marcus Smolka, assistant professor of molecular biology and genetics. The findings are detailed in the July 30 edition of the journal Molecular Cell.

Previous studies have shown that cells lacking Mec1 accumulate damaged DNA and become more sensitive to agents that interfere with replication. The researchers report that the Mec1 protein monitors and repairs the machinery responsible for replicating the DNA. At times, when DNA becomes damaged, the replication machinery can actually detach from the DNA -- like a train coming off a track -- but Mec1 coordinates the repair of the machinery and the DNA itself, allowing it to restart and continue replicating.

"Mec1 organizes the cell's response against things that jeopardize the integrity of the genome," Smolka said.

During the replication process, Mec1 accumulates at trouble spots such as in the DNA or other blocks to replication. Mec1 is known as a kinase, a type of enzyme that modifies other proteins by adding a phosphate group to them (a process called phosphorylation), which then leads to a functional change in the protein. The researchers report that Mec1 adds a phosphate group to a protein known as Slx4, which then triggers Slx4 to anchor to the replication machinery. Slx4 then can employ a variety of tools to repair DNA and the replication machinery.

The findings are important because researchers have discovered counterparts (called orthologues) to Mec1, other related proteins with similar biological pathways in humans. Also, to the human that produce Mec1 and related proteins can lead to cancer predisposition and neurological disorders. At the same time, cancer cells employ their own similar replication repair system, so understanding the process may help researchers design interventions that interrupt replication of cancer DNA.

Recently, other researchers discovered that the human version of Mec1, called ATR, phosphorylates a protein that is the human counterpart to Slx4. The next step, Smolka said, will be to see if after phosphorylation the human Slx4 also anchors to the machinery to repair any damaged machinery or DNA.

Co-authors include Patrice Ohouo, a graduate student in biochemistry, molecular and cell biology; Francisco M. Bastos de Oliveira, a postdoctoral researcher; and Beatriz Almeida, a research support specialist; all members of Smolka's lab.

Explore further: Where’s the Starting Point? Researchers try to unravel the mystery of DNA Replication During Cell Division

Related Stories

Chromatin remodeling complex connected to DNA damage control

August 9, 2007

When molecular disaster strikes, causing structural damage to DNA, players in two important pathways talk to each other to help contain the wreckage, scientists at The University of Texas M. D. Anderson Cancer Center report ...

Penn researchers discover new mechanism for viral replication

August 16, 2007

Researchers at the University of Pennsylvania School of Medicine have identified a new strategy that Kaposi’s Sarcoma Associated Herpesvirus (KSHV) uses to dupe infected cells into replicating its viral genome. This allows ...

Recommended for you

Plastic in 99 percent of seabirds by 2050

August 31, 2015

Researchers from CSIRO and Imperial College London have assessed how widespread the threat of plastic is for the world's seabirds, including albatrosses, shearwaters and penguins, and found the majority of seabird species ...

Researchers unveil DNA-guided 3-D printing of human tissue

August 31, 2015

A UCSF-led team has developed a technique to build tiny models of human tissues, called organoids, more precisely than ever before using a process that turns human cells into a biological equivalent of LEGO bricks. These ...

Study shows female frogs susceptible to 'decoy effect'

August 28, 2015

(Phys.org)—A pair of researchers has found that female túngaras, frogs that live in parts of Mexico and Central and South America, appear to be susceptible to the "decoy effect." In their paper published in the journal ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.