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DNA repair in mammal embryos is a matter of timing

taxia telangiectasia. This new work points to the specific DNA repair pathway that ATM is required to monitor in order to prevent neurodegeneration.

The HR pathway fixes a broken chromosome by using that chromosome's exact "twin" as a blueprint to guide the repair job, according to Peter McKinnon, Ph.D., an associate member of Genetics and Tumor Cell Biology at St. Jude and senior author of the PNAS paper. However, such twins only exist in cells that are preparing to divide into two new cells, a process called mitosis, he noted. Then, as the cell starts to divide, each member of the sister chromatid pair moves into a different new cell.

Because HR is active only during the first half of embryo development, it is the critical repair pathway for the rapidly multiplying precursor and stem cells--cells that populate the body during early development with "daughter" cells--that later take on specific roles, according to researchers.

"Therefore, if HR-related apoptosis is blocked during the early part of embryo development, precursor and stem cells are affected. And since those cells give rise to many different types of cells and tissues, many different types of cancers can arise, such as skin cancer and sarcomas (cancers of bone, cartilage, fat, muscle or blood vessels)," McKinnon said.

But as cells acquire specialized structures and functions, they stop dividing and no longer produce sister chromatids. "When cells begin assuming specific roles in the brain, they stow away most of their chromosomes into tightly wrapped strings of DNA and use only those genes required to survive and allow them to perform these roles," McKinnon explained. "In the absence of sister chromatids to use as blueprints, the NHEJ repair pathway uses various chemical means to join the broken ends of DNA strands."

Since the cell uses NHEJ only when many cells are becoming specialized, cancers that arise in the absence of this pathway are more specific, suc
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Contact: Bonnie Kourvelas
media@stjude.org
901-495-3306
St. Jude Children's Research Hospital
19-Jun-2006


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