Thursday, November 21, 2013

Recently discovered enzyme found to play a role in DNA repair

DNA ligase I repairing chromosomal damage
Courtesy of Tom Ellenberger
Every time a new cell is formed the parent cell must first make of copy of its DNA that it will pass along to the daughter cell in a process called replication. When DNA damage is encountered the progress of DNA replication is halted which can lead to DNA double strand breaks and threaten genomic stability. The final result of genomic instability is cell death.

In order restart DNA replication and repair DNA damage the cell has two options if it proceeds with replication: either perform an error prone synthesis of the damaged DNA or skip the damage and reinitiate DNA replication beyond the damage. The unreplicated gap can then be repaired after replication.

A recent paper published in Nature Structural & Molecular Biology entitled: 'Repriming of DNA synthesis at stalled replication forks by human PrimPol' describes how the recently discovered enzyme PrimPol uses its primase activity to continue replication progression and reinitiate DNA synthesis. Thus, PrimPol allows cells to survive but it will introduce mutations into DNA at a higher rate than normal.

This paper is the work of a group Spanish scientist who previously reported their discovery of PrimPol and characterized its biochemistry. They have also found that this enzyme is related to proteins found in archaebacteria which means it is a very old enzyme in evolutionary terms since archaebacteria are among the first life forms to inhabit earth. Archaebacteria are characterized by their ability to survive in harsh environmental conditions. These harsh conditions result in more extensive DNA damage so having an enzyme like PrimPol would be beneficial even though it can't duplicate DNA as precisely as other enzymes. The authors postulate that this inexact replication may be important for the evolution of genomes.

These scientists are now investigating the possible role of PrimPol in diseases such as cancer where DNA damage leads to mutations which lead to abnormal growth. It is not unreasonable to speculate that PrimPol, which is involved DNA damage repair but also leads to mutations, could have a role in cancer.

Some information for this blog post was obtained from the Science Daily article: Newly Discovered Ancestral Enzyme Facilitates DNA Repair