COMMENTARY DNA repair and transcriptional activity in genes

Recent findings on the genomic heterogeneity of mammalian DNA repair have disclosed new features about molecular aspects of the repair processes and have also raised new interesting questions to help direct our research. The studies on preferential DNA repair in active genes demonstrate that there are variations in the repair processes corresponding to different parts of the genome and we are now attempting to study how these processes are regulated or controlled. In this commentary, it seems pertinent to discuss an important aspect of the preferential DNA repair mechanisms, the potential relationship between the DNA repair efficiency, the local chromatin structure and the transcriptional activity for a specific mammalian gene. Most of the available results on DNA repair in specific genomic sequences are based on a technique to measure damage and repair after ultraviolet (u.v.) irradiation using quantitative hybridization (Bohr et al. 1985; Bohr & Okumoto, 1988) and have been reviewed recently (Bohr et. al. 1987). The initial findings were that the essential, active gene dihydrofolate reductase (DHFR) was preferentially repaired in hamster and human cells (Bohr et. al. 1985; Mellon et al. 1986), and some results have been outlined in Table 1. The fine structure of DNA repair in and around the DHFR gene in CHO cells has been examined, and it was found that the preferential DNA repair was confined to a genomic region of about 60-80 kilobases. This region has been called a DNA repair domain and its size corresponds well with described higher order structures or loops in chromatin (Bohr et al. 1986). However, further studies are needed to clarify whether DNA repair is regulated within such loops in chromatin. Different genes are repaired with different efficiency. In a study on the repair of proto-oncogenes in mouse cells, it was reported (Madhani et al. 1987) that the c-abl proto-oncogene is repaired five times more efficiently than the c-mos proto-oncogene in the same cells (Table 1). Since the c-abl gene is actively transcribed and the cmos gene is not, these findings indicate that a correlation exists between DNA repair efficiency and transcriptional activity. However, the c-abl gene is directly involved in the translocation leading to chronic myelogenous leukaemia whereas the c-mos gene is only indirectly associated with the translocation leading to acute myeloid leukaemia. This raises the alternative possibility that