Editorial Feature

"CYREN" Protein Helps Cells Decide the Right Path for DNA Repair

Double strand breaks (DSB) within DNA are a common and natural occurrence within the eukaryotic cell.

However, this biological reaction can also result from the cell’s own metabolites such as reactive oxygen species (ROS), as well as any harmful exposure of the cell to irradiation, chemical agents or ultraviolet (UV) light within the environment.

Luckily, our genetic material is equipped with two major pathways that are responsible for repairing such breaks within our DNA. Homologous recombination (HR) is the first type of DNA repair process that involves a series of interrelated pathways that check the entire genome, base by base, for the presence of lesions that could affect the future replication and transcription of a new DNA strand.

The second way in which DSB are repaired is through nonhomologous DNA end joining (NHEJ), which is a faster enzymatic process that resects damaged DNA, utilizes polymerases to fill-in new DNA, and finally restores the integrity of a new DNA strand by a functional ligase1.

During the G1 phase, NHEJ plays a dominant role in repairing DNA breakage, however, during the other phases of the cell cycle the role of HR appears to be more prominent. While it is unclear how the choice is made to repair a DSB by either mechanism, NHEJ is generally considered to be a more efficient repair pathway, however, its rapid pace can result in the joining of two incorrect strand ends, which can have disastrous results for the organism.

In an effort to further understand the decision by which NHEJ is chosen over HR, a recent study conducted by Scientists at the Salk Institute for Biological Studies in California have discovered a microprotein called CYREN, which is responsible for choosing which DNA repair pathway is most appropriate. To test this theory, the Researchers studied the CYREN protein, which was originally identified as a potential modulator of retroviral infection, and how its binding to the Ku70/80 heterodimer plays a role in this process.

The Researchers focused on the telomere, a region present at the end of the chromosome where fusion typically occurs, and investigated the role that CYREN plays on the replication process at this level. Through confirmatory studies involving chromosome-oriented fluorescence in situ hybridization (FISH), the Researchers determined that without CYREN present at the telomere site, the Ku70/80 protein was activated, thereby initiating the copying of DNA strands.

When CYREN was present at the telomere, the Researchers found that this protein inhibited Ku70/80 which subsequently prevented any DNA strands from being copied. Further molecular investigation of the role of the CYREN protein at the telomere determined that the CYREN protein directly attaches to Ku70/80 to inhibit NHEJ within the cell, however, this process is dependent upon what stage of the cell cycle the breakage occurs.

More specifically, the binding of CYREN to the Ku70/80 heterodimer has a preferential inhibition to break with strand overhangs, which was a consistent observation present at the telomere region.

The discovery of the CYREN protein not only offers Researchers a greater understanding of the complexity of the DNA repair pathway, but could also be the source of cancer initiation and potential treatment options in the future. CYREN, which stands for cell cycle regulator of NHEJ, is described by the Authors as a cell-cycle specific inhibitor of NHEJ.

Additionally, the genotoxic potential of many drugs and environmental toxicants can also be further studied by the discovery of the role of the CYREN protein in the DNA repair process, as these often error-prone repair areas of genetic material are most susceptible to long term effects when attacked by these agents.

Image Credit:

nexusby/ Shutterstock.com

References:

  1. “Comparison of nonhomologous end joining and homologous recombination in human cells” Z. Mao, M. Bozzella, et al. DNA Repair. (2008). DOI: 10.1016/j.dnarep.2008.06.018.
  2. “Regulation of DNA repair pathway choice in S and G2 Phases by the NHEJ inhibitor CYREN” N. Arnoult, A. Correia, et al. Nature. (2017). DOI: 10.1038/nature24023.

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Comments

  1. Aries Qin Aries Qin Taiwan says:

    The genotoxic potential of many drugs and environmental toxicants can also be further studied by the discovery of the role of the CYREN protein in the DNA repair process, as these often error-prone repair areas of genetic material are most susceptible to long term effects when attacked by these agents.  Concrete Mixer Truck Price  [email protected]

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of AZoNano.com.

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