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Kub5-Hera, the human Rtt103 homolog, plays dual functional roles in transcription termination and DNA repair.

Nucleic acids research, 2014

Kub5-Hera, the human Rtt103 homolog, plays dual functional roles in transcription termination and DNA repair.
Functions of Kub5-Hera (In Greek Mythology Hera controlled Artemis) (K-H), the human homolog of the yeast transcription termination factor Rtt103, remain undefined.
Here, we show that K-H has functions in both transcription termination and DNA double-strand break (DSB) repair.
K-H loss resulted in increased basal R-loop levels, DSBs, activated DNA-damage responses and enhanced genomic instability.
Significantly lowered Artemis protein levels were detected in K-H knockdown cells, which were restored with specific K-H cDNA re-expression.
K-H deficient cells were hypersensitive to cytotoxic agents that induce DSBs, unable to reseal complex DSB ends, and showed significantly delayed γ-H2AX and 53BP1 repair-related foci regression.
Artemis re-expression in K-H-deficient cells restored DNA-repair function and resistance to DSB-inducing agents.
However, R loops persisted consistent with dual roles of K-H in transcription termination and DSB repair.