Phosphoregulation in the reversal of DNA damage checkpoints

Abstract

The process of cell division is fundamental to all life. From bacteria to man, any new cell can only arise by division of a preexisting cell. The adult human body is a product of trillions of cell division events and cell division remains essential in most organs to replenish cells during life. All cells except those that give rise to spermatocytes and oocytes must divide in such a way that the two arising daughter cells inherit identical copies of the genetic material encoded in the DNA. This most basic function of cell division is achieved by first accurately duplicating the DNA of the individual chromosomes and then equally segregating the copies over the two arising daughter cells. This sequence of events can be repeated as necessary and is known as the cell cycle. Damage to the DNA endangers the faithful transmission of genetic material to daughter cells, as damaged DNA cannot be correctly copied and broken fragments of chromosomes cannot be segregated. The initiation of DNA duplication and chromosome segregation are therefore blocked by the presence of damaged DNA and this block must be relieved once the DNA has been repaired. The resumnption of the cell cycle after a DNA damage-induced arrest and the molecular signals that control this process are the subject of this thesis.