Double-strand breaks and translocations in cancer.
The correct repair of double-strand breaks (DSBs) is essential for the genomic integrity of a cell, as inappropriate repair can lead to chromosomal rearrangements such as translocations. In many hematologic cancers and sarcomas, translocations are the etiological factor in tumorigenesis, resulting in either the deregulation of a proto-oncogene or the expression of a fusion protein with transforming properties. Mammalian cells are able to repair DSBs by pathways involving homologous recombination and nonhomologous end-joining. The analysis of translocation breakpoints in a number of cancers and the development of model translocation systems are beginning to shed light on specific DSB repair pathway(s) responsible for the improper repair of broken chromosomes.
Elliott
B
B
Cell Biology Program, Memorial Sloan-Kettering Cancer Center and Cornell University, Graduate School of Medical Sciences, New York, NewYork 10021, USA.
Jasin
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M
D002051:Burkitt Lymphoma / Q000235:genetics; D018288:Carcinoma, Small Cell / Q000235:genetics; D004249:DNA Damage; D004260:DNA Repair; D015321:Gene Rearrangement; D019337:Hematologic Neoplasms / Q000235:genetics; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics; D008957:Models, Genetic; D009369:Neoplasms / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D014178:Translocation, Genetic