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Peter J. McKinnon, PhD
St. Jude discovery gives hints to origin of many cancers
St. Jude investigators have discovered that the DNA repair pathway called homologous recombination (HR) works primarily during the first half of embryo development, when many cells are dividing inside the growing body. In contrast, the pathway called non-homologous end joining (NHEJ) becomes an important repair mechanism midway through development of the body, when cells begin to assume their final form.
The team also showed that blocking a repair pathway causes the cell to commit suicide (apoptosis), and that preventing this suicide keeps the damaged cell alive and able to become cancerous. Moreover, the type of cancer that develops depends on which repair pathway was originally disrupted. A report on these results appears in the online prepublication issue of Proceedings of the National Academy of Science.
Because HR is the critical repair pathway for the rapidly multiplying precursor cells that give rise to many different types of cells and tissues, disrupting HR-linked apoptosis can lead to many different types of cancers, such as skin cancer and sarcomas, according to Peter McKinnon, PhD, Genetics and Tumor Cell Biology. And since the cell uses NHEJ only when many cells are becoming specialized, cancers that arise in the absence of this pathway are more specific, such as cancer of a type of cell that produces only immune cells called B lymphocytes.
Other authors of the report include Kenji Orii and Naomi Kondo (formerly of St. Jude; now at Gifu University School of Medicine, Japan) and Youngsoo Lee, PhD, Genetics and Tumor Cell Biology.