MicroRNA responses and stress granule formation modulate the DNA damage response.
DNA damage induced by UV irradiation provokes profound changes in gene expression. Both transcriptional regulation and posttranslational modification of proteins have been known for many years, but the involvement of microRNAs in regulation of mRNA translation has been described only recently. This level of gene expression regulation appears to operate at the intermediate time points between fast protein modifications (within minutes) and much slower transcriptional reprogramming (which takes several hours to days to develop). MicroRNAs most clearly contribute to regulation of cell cycle checkpoints and apoptosis, but may also influence other aspects of cellular metabolism, differentiation and proliferation. Interestingly, the RNA silencing machinery redistributes into cytoplasmic RNA granules, termed stress granules (SGs), in cells that go through mitosis after UV irradiation. We discuss the implications of these findings for our understanding of the DNA damage response.
Pothof
Joris
J
Department of Cell Biology and Genetics, Erasmus MC, University medical center Rotterdam, Rotterdam, The Netherlands.
Verkaik
Nicole S
NS
Hoeijmakers
Jan H J
JH
van Gent
Dik C
DC
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D003594:Cytoplasmic Granules / Q000378:metabolism*; D004249:DNA Damage; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D020868:Gene Silencing / Q000502:physiology; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D013312:Stress, Physiological / Q000235:genetics / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D020687:cdc25 Phosphatases / Q000378:metabolism*
D035683:MicroRNAs; D016159:Tumor Suppressor Protein p53; D011494:Protein Kinases; D020687:cdc25 Phosphatases