Essential Function of Dicer in Resolving DNA Damage in the Rapidly Dividing Cells of the Developing and Malignant Cerebellum

• DOI: 10.1016/j.celrep.2015.12.037
• Publication Date: 2015-12-31T18:53:13Z
• Authors: Vijay Swahari; Ayumi Nakamura; Jeanette Baran-Gale; Idoia Garcia; Andrew J. Crowther; Robert Sons; Timothy R. Gershon; Scott Hammond; Praveen Sethupathy; Mohanish Deshmukh
• Keywords: Dicer

Maintenance of genomic integrity is critical during neurodevelopment, particularly in rapidly dividing cerebellar granule neuronal precursors that experience constitutive replication-associated DNA damage. As Dicer was recently recognized to have an unexpected function the damage response, we examined whether important for preserving developing brain. We report deletion mouse cerebellum resulted accumulation leading progenitor degeneration, which rescued with p53 deficiency; DGCR8 also similar and degeneration. deficiency death other cells including embryonic stem malignant progenitors a model medulloblastoma. Together, these results identify essential resolving spontaneous occurs rapid proliferation developmental cells.