The normal unwinding of DNA is critical under many particular circumstances, for example during replication. There are hundreds of different types DNA helicases in human cells, and each unwinds DNA under different circumstances. Although it is important to keep the strands of DNA together most of the time, if they can't be unwound when needed, serious problems could occur.
The Penn researchers hope to eventually explore the role of G4 capping in human aging after they know more about the G4 cap in yeast cells, which are easy to study because they can be engineered to make very specific changes in their DNA and proteins.
Recently, Johnson's group found that DNA sequences with the potential to form G4 DNA, which exist not only at telomeres but also at many locations throughout the entire human genome, are closely connected to changes in gene expression in cells from people with Werner or Bloom syndrome. They predict that G4 DNA abnormalities also exist at the telomeres in these human diseases and perhaps those of aging cells.
In their experiments in which telomeres were specifically examined in yeast, both elevated levels of G4 binding protein and inactivation of the yeast helicase that is similar to the one missing in human Werner and Bloom syndrome patients led to increased protection of the telomeres. This suggested that the G4 caps were present on the telomeres and that they protected the telomere from breaking down.
The overall role of G4 DNA is not simple and might seem to be contradictory. For example, work from several other research groups has suggested that G4 DNA can interfere with the replication and capping of telomeres, in contrast to the protective role observed by Johnson's group.
"This points out the complexity of G4 DNA," said Johnson. "On one hand, s
|Contact: Karen Kreeger|
University of Pennsylvania School of Medicine