Knowing where PARP-1 is located and how it works may allow scientists to target this protein while battling common human diseases.

Their research is in a study published (Feb.8, 2008) in the journal Science.

"This finding was unexpected -- especially since it entails a broad distribution of PARP-1 across the human genome and a strong correlation of the protein binding with genes being turned on," said W. Lee Kraus, Cornell associate professor in molecular biology and the corresponding author in the published study. Kraus has a dual appointment at Cornell's Weill Medical College in New York City. "Our research won't necessarily find cures for human diseases, but it provides molecular insight into the regulation of gene expression that will gives us clues where to look next."

Kraus explains that PARP-1 and another genome-binding protein called histone H1 compete for binding to gene "promoters" (the on-off switches for genes) and, as such, act as part of a control panel for the human genome. H1 puts genes in an "off" position and PARP-1 turns them "on." The new study, said Kraus, shows that for a surprising number genes, the PARP-1 protein is present and histone H1 is not, helping to keep those genes turned on.

When human cells are exposed to physiological signals, such as hormones, or to stress signals, such as metabolic shock or DNA damage caused by agents like ultra-violet (UV) light, the cells take action. One of the cellular responses is the production of NAD (nicotinamide adenine dinucleotide), a metabolic communication signal. NAD promotes the removal of PARP from the genome and alters PARP-1's ability to keep genes on, the scientists have found.

Knowing where this component of the genome's control panel -- the PARP-1 protein -- is located, scientists can better understand the effects of synthetic chemical inhibitors of PARP-1 activity, which are being explored for the treatment of human diseases including stroke, heart disease and cancer. Thus, conceivably, when a patient is having stroke, it may one day be possible to use PARP-1 inhibitors as part of stroke therapy, or one day play a role in targeting cancer, says Kraus.

"Think of PARP-1 as a key regulator of gene expression in response to normal signals and harmful stresses," said Kraus. "If you could control most of the traffic lights in a city's street grid with one hand, this is analogous to controlling gene expression across the genome with PARP-1. Under really adverse conditions, you can set all the lights to stop."

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Energy could be stored in the base without competing with any other part of the plant for photosynthesis, as the rest only makes chlorophyll a. Also, the altered corn using the chlorophyll d gene could become a super plant because of its enhanced ability to harness energy from the Sun.

That model is similar to how Acaryochloris marina actually operates in the South Pacific, specifically Australia's Great Barrier Reef. Discovered just 11 years ago, the cyanobacterium lives in a symbiotic relationship with a sponge-like marine animal popularly called a sea squirt. The Acaryochloris marina lives beneath the sea squirt, which is a marine animal that lives attached to rocks just below the surface of the water. The cyanobacterium absorbs red edge light through the tissues of the sea squirt.

The genome, said Blankenship, is fat and happy. Acaryochloris marina lies down there using far red light that no one else can use. The organism has never been under very strong selection pressure to maintain a modest genome size. It's in kind of a sweet spot. Living in this environment is what allowed it to have such dramatic genome expansion.

Touchman said that once the gene that causes the late-step chemical transformation is found and inserted successfully into other plants or organisms, that it could potentially represent a five percent increase in available light for organisms to use.

We now have the complete genetic information of a novel organism that makes this type of pigment that no other organism does, he said. We don't yet know what every gene does, but this presents a fertile area for future studies. When we find the chlorophyll-d enzyme and then look into transferring it into other organisms, we'll be working to extend the range of potentially useful radiation from our Sun.

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