On Friday February 1st, Petra Langerak will defend her thesis entitled “DNA Damage Tolerance: From Error Free UV-Damage Bypass to Mutagenesis of Immunoglobulin Genes” to receive the degree of doctor at the University of Amsterdam, at 12.00 hrs in the Agnietenkapel.
When a cell is exposed to damaging agents, such as ultraviolet light, the DNA can become damaged. This can have terrible consequences, ranging from DNA breaks to cell death.
Special enzymes called TLS polymerases can protect the cell against the harmful consequences. Although the use of TLS polymerases is beneficial for a cell in the presence of DNA damage, misuse can lead to the introduction of mistakes in the DNA.
It is therefore wise to limit the use of these enzymes. The main question that is answered in this thesis explains how this use is regulated. It is shown that PCNA, a molecule that binds polymerases and keeps them at the DNA to allow them to perform their function, is very important. When it is useful to activate TLS polymerases, PCNA becomes “flagged” with an ubiquitin molecule. The combination of PCNA with ubiquitin is recognized by TLS polymerases, leading to their activation.