Cell Cycle and DNA Damage Response in Postmitotic Neurons

摘要: Cellular DNA copes with constant exposure to different hazards, environmental and intrinsic. This leads lesions which interfere transcription replication if not repaired or incorrectly, can produce mutations large-scale genome aberrations that may lead cell malfunction death contribute pathologies (Jackson, 2009; Sancar et al., 2004). For this reason, virtually every organism is equipped highly conserved surveillance network known as the damage response (DDR) whose function sense activate several downstream pathways, including cycle checkpoints, repair apoptotic signaling (Rouse & Jackson, 2002; Zhou Elledge., 2000). The DDR has been investigated mainly in mitotic cells, checkpoints are a major contributor DDR, required for (Stracker 2008). Not much about postmitotic neurons. It known, however, all eukaryotic systems operating proliferating cells also operate neurons (Fishel 2007; Lee McKinnon, Sharma, Weissman Wilson, McNeill, 2007) dysfunctional plays an important role neurodegeneration associated syndromes (e.g. ataxia telangiectasia) characterized by neurological abnormalities (Barzilai, 2010; Rass Shiloh, 2003, 2006). suggests importance of While part involved repair, signaling, fate decisions their contribution remains unclear. Nonetheless, evidence accumulates damage-initiated apoptosis signaling. Recently, we have demonstrated activation (Tomashevski 2010). expression cell-cycle markers (Schmetsdorf 2007, 2009) activity (Sharma, observed brain under physiological conditions repair. involvement machinery both potential these cells. review focuses on context what