Impact of DNA base lesion repair for stem cell maintenance

DNA damage (mutations) are the fundamental cause of all forms of cancer and a number of different but integrated processes operate to prevent genetic changes from occurring. These include cell cycle regulation, DNA replication, transcription, DNA repair, regulation and sanitation of nucleotide pools, enzymatic inactivation of mutagens, DNA recombination, immune responses and apoptosis. Deficiencies in DNA repair are associated not only with cancer and aging but also with stem cells defects. Genome mainten ance in stem cells is essential for self-renewal and the capacity to differentiate. Several lines of evidence suggest that stem cells maintain genomic integrity better than somatic cells. Gene expression studies indicate that a small number of genes are c onsistently overexpressed in stem cell populations including a surprisingly high proportion of DNA repair genes. The main goal of studying stem/progenitor cell populations is to gain a better understanding of the significance of genome maintenance, with e mphasis on repair mechanisms removing base lesions in DNA. Stem cells with damaged genomes can undergo apoptosis or forced differentiation, which result in stem cell failure syndromes, aplasia and transformation. A long-term goal is to work towards health y stem cells populations for therapeutic purposes that maintain genomic stability. This is particularly important for investigating the viability of stem cells prior to transplantation.