**2. DNA damage checkpoints**

To maintain genomic integrity and faithful transmission of fully replicated and undamaged DNA during cell division, eukaryotic organisms evolved a complex DNA surveillance program (Reihardt & Yaffe, 2009). Apart from DNA repair mechanisms mentioned above, DNA damage response represents a complex network of multiple signaling pathways involving cell cycle checkpoints, transcriptional regulation, chromatin remodeling and apoptosis (Dai & Grant, 2010; Danielsen et al., 2009). In response to DNA damage, eukaryotic cells activate a complex protein kinase-based signaling network to arrest progression through the cell cycle. Activation of signaling cascade recruits repair machinery to the site of DNA damage, provides time for repair or if the genotoxic insult exceeds repair capacity, additional signaling pathways leading to cell death, presumably *via* apoptosis, are activated (Reinhardt et al., 2010; Reinhardt & Yaffe, 2009). When DNA damage occurs, distinct, albeit overlapping and cooperating checkpoint pathways are activated, which block S phase entry (the G1/S phase checkpoint), delay S phase progression (the S phase checkpoints) or prevent mitotic entry (the G2/M phase checkpoint). The primary G1/S cell cycle checkpoint controls the commitment of eukaryotic cells to transition through G1 phase and enter DNA synthesis phase. In G1 phase, cells have to make a decision between continuing proliferation or exiting the cell cycle to become quiescent differentiated, senescent or apoptotic (Dijkstra et al., 2009). The S phase checkpoints are activated when DNA damage occurs during DNA synthesis, or when DNA replication intermediates accumulate. Depending on the type and magnitude of damage, cells activate one of three distinct S phase checkpoint pathways: an intra-S phase checkpoint induced by double strand breaks, a replication checkpoint by the stalled replication fork and the S/M checkpoint blocking premature mitosis. The S/M checkpoint differs from the well-defined G2/M checkpoint. The S/M checkpoint is ATM-independent, it is measurable only several hours after DNA damage and is initiated in cells that were in S phase at the time of insult (Hurley & Bunz, 2009; Rodriguez-Bravo et al., 2007). When cells encounter DNA damage in G2, the G2/M checkpoint stops the cell cycle to prevent the cell from entering mitosis. Defects in cell cycle arrest at the respective checkpoint are associated with genome instability and oncogenesis (Houtgraaf et al., 2006).
