NBS1 Functions as a Multifaceted Protein in DNA Damage Repair and Gametogenesis

Abstract

Proper maintenance of the genome is crucial for survival of all organisms. It is of major importance for reproduction and development, that the information encoded in the genome is replicated correctly. However, endogenous and exogenous DNA-damaging agents are constantly threatening the integrity of the genome. When a cell detects damage, it can arrest the cell cycle at specific checkpoints (G1/S, G2/M and intra-S). The activation of cell cycle checkpoints provides time to repair DNA lesions before they can be converted into permanent mutations. Incorrect repair or accumulation of DNA damage results in genome instability, which may lead to impaired functioning of the cell and even to the development of cancer. Therefore, all organisms have a complex network of DNA repair mechanisms, each of which is able to repair a subset of lesions. The biological significance of DNA repair mechanisms is underlined by the large number of repair genes, many of which are conserved from yeast to humans. The importance of the DNA repair pathways is also emphasized by the fact that defects in DNA repair genes often lead to cancer predisposition in humans. When DNA damage cannot be repaired properly, the cell can either go into apoptosis or can contribute to ageing.