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DNA ends: Common tool, different job

Every time a cell repairs or replicates its DNA, the resulting single strand is wrapped up by a dedicated protein complex. In eukaryotes or organisms whose cells have a nucleus, this job is handled by a tripartite complex called replication protein A (RPA). Researchers at the Salk Institute for Biological Studies have now unearthed a novel RPA-like complex that specifically homes in on the short single-stranded DNA "tail" end of yeast chromosomes.

Their findings, reported in the online edition of Nature Structural & Molecular Biology, will help scientists to better understand the dynamics that keep chromosomes ends, called telomeres, intact.

"Identification of this new RPA-like complex, which is targeted to a specific region of the genome, suggests that multiple RPA-like complexes have evolved, each making individual contributions to genomic stability," says the study's lead author Vicki Lundblad, Ph.D., a professor in the Molecular Cell Biology Laboratory at the Salk Institute.

With each round of cell division, telomeres ?long stretches of repetitive DNA ?erode a little bit further. Some have likened this progressive shortening to a genetic biological clock that winds down over time. In fact, when telomeres reach a "critical length," the cell can no longer multiply ?a characteristic sign of cellular senescence.

In certain cells, such as our germ cells or baker's yeast cells, which need to divide indefinitely, an enzyme called telomerase elongates telomeres to compensate for the continual attrition at chromosome ends. At the same time, telomerase activity is the main mechanism by which human tumor cells achieve immortal growth.

In addition, the natural ends of chromosomes could potentially look like broken strands of DNA that a cell's repair machinery is designed to fix. This has been a long-standing puzzle, because mending chromosome ends as though they were double-strand breaks would result in either unregulated
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Source:Salk Institute


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