Uncovering How Perfect Copies Are Made
Prior to each cell division, the DNA molecule must be duplicated so that mother and daughter cell receive the same genetic information. Errors in replication can lead to cancer, among other diseases. How does the cell ensure the required precision and prevent errors? Boris Pfander and his team seek to find an answer to this question by investigating the control mechanisms of DNA replication.
The molecular machinery in the cell nucleus is constantly confronted with a major challenge: Prior to the actual cell division, the DNA has to be duplicated one-to-one so that two identical copies for mother and daughter cell are produced. Duplication begins from a variety of starting points, activated in a precisely orchestrated sequence. In order for DNA replication to proceed in such an accurate way, it has to be regulated very strictly. Errors change the DNA’s sequence, and cancer or other severe diseases can occur.
Defects are detected
Boris Pfander and his colleagues study the mechanisms of DNA replication and want to uncover how they are linked to other cellular processes. Correct replication, for example, would not be possible without DNA repair. Defects in the DNA often lead to the assembly of a wrong building block during duplication. The cell solves this problem with checkpoint mechanisms: They identify damage to the DNA and then stop replication.
One protein, two functions
Pfander is particularly interested in the protein Dpb11. Together with other proteins, Dpb11 initiates the formation of the molecular replication machinery (replisome). Furthermore, it interacts with the checkpoint proteins. Hence, Dpb11 is the molecular link between the initiation of replication and the checkpoint mechanisms. Its elucidation could therefore also help to decode the interaction of these processes.