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

Nucleic Acids Research (Impact Factor: 9.11). 03/2014; 42(8). DOI: 10.1093/nar/gku160
Source: PubMed


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 forms distinct protein complexes with factors that repair DSBs (e.g. Ku70, Ku86, Artemis) and terminate
transcription (e.g. RNA polymerase II). 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.

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Available from: Julio C. Morales, Mar 05, 2014
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    • "Importantly, co-Immuno-Precipitation (Co-IP) analyses using a K-H-specific antibody generated in our lab that recognizes K-H, but not the closely related p15RS protein, revealed that K-H associated with Ku70 and Artemis. This association was not dependent on DNA interaction, since it was observed in the presence or absence of ethidium bromide (Morales et al., 2014). Moreover, we showed that K-H, Ku70, Ku86 and Artemis are present in higher molecular weight protein complexes separate from RNAPII (Morales et al., 2014). "
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