The role of DNA breaks in genomic instability and tumorigenesis
Article first published online: 7 JUL 2003
Volume 194, Issue 1, pages 77–95, August 2003
How to Cite
Mills, K. D., Ferguson, D. O. and Alt, F. W. (2003), The role of DNA breaks in genomic instability and tumorigenesis. Immunological Reviews, 194: 77–95. doi: 10.1034/j.1600-065X.2003.00060.x
- Issue published online: 7 JUL 2003
- Article first published online: 7 JUL 2003
Summary: DNA double-strand breaks (DSBs) represent dangerous chromosomal lesions that can lead to mutation, neoplastic transformation, or cell death. DSBs can occur by extrinsic insult from environmental sources or may occur intrinsically as a result of cellular metabolism or a genetic program. Mammalian cells possess potent and efficient mechanisms to repair DSBs, and thus complete normal development as well as mitigate oncogenic potential and prevent cell death. When DSB repair (DSBR) fails, chromosomal instability results and can be associated with tumor formation or progression. Studies of mice deficient in various components of the non-homologous end joining pathway of DSBR have revealed key roles in both the developmental program of B and T lymphocytes as well as in the maintenance of general genome stability. Here, we review the current thinking about DSBs and DSBR in chromosomal instability and tumorigenesis, and we highlight the implications for understanding the karyotypic features associated with human tumors.