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KUB5/HERA: a dual acting protein that suppresses genomic instability and promotes DNA repair after low dose IR exposure

Julio C. Morales
University of Texas Southwestern Medical Center

Abstract

Eukaryotic cells can respond to DNA double strand breaks created by low doses of IR by activating homologous recombination (HR) or non-homologous endjoining (NHEJ) pathways to repair DNA. A yeast two-hybrid screen using Ku70 as bait uncovered an evolutionarily conserved protein, Kub5/Hera, homologous to the yeast rtt103 gene, that when altered in both yeast and mammalian cells led to increased IR sensitivity and DNA repair defects. In human cells, we showed that decreased levels of this protein lead to endogenous basal level increased DNA damage responses (DDR) and chromosomal aberrations. After low doses of IR (≥10 cGy) we observed differences in survival between cells with normal and decreased kub5/hera protein levels. The endogenous DDR noted in unperturbed kub5/hera shRNA knockdown or kub5/hera+/- MEF cells may be due to the formation of RNA:DNA hybrids, suggesting a conservation between KUB5/HERA and rtt103 transcription termination function, in addition to a role in DSB repair. | PDF Version

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