Abstract
The DNA dependent protein kinase (DNA-PK) is a trimeric nuclear complex consisting of a large protein kinase and the Ku heterodimer. The kinase activity of DNA-PK is required for efficient repair of DNA double-strand breaks (DSB) by non-homologous end joining (NHEJ). We also showed that the kinase activity of DNA-PK is essential for post-integrational DNA repair in the case of HIV-1 infection. Besides, DNA-PK is known to participate in such cellular processes as protection of mammalian telomeres, transcription, and some others where the need for its phosphorylating activity is not clearly elucidated. We carried out a systematic search and analysis of DNA-PK targets described in the literature and identified 67 unique DNA-PK targets phosphorylated in response to various in vitro and/or in vivo stimuli. A functional enrichment analysis of DNA-PK targets and determination of protein–protein associations among them were performed. For 27 proteins from these 67 DNA-PK targets, their participation in the HIV-1 life cycle was demonstrated. This information may be useful for studying the functioning of DNA-PK in various cellular processes, as well as in various stages of HIV-1 replication.
Highlights
DNA-dependent protein kinase (DNA-PK) is a heterotrimeric complex that consists of Ku70(XRCC6), Ku80 (XRCC5), and DNA-PKcs (PRKDC)
DNA-PK complex acts both as a scaffold platform for non-homologous end joining pathway (NHEJ) participants (XLF, XRCC4, APLF, Ligase IV, etc.) that are essential for synapsis formation, end-processing, and ligation and as a kinase that modifies chromatin around the double-strand break (DSB), regulates the activity of repair factors as well as promotes DNA-PK disassembly from
We previously showed that the phosphorylating activity of DNA-PKcs was necessary for HIV-1 post-integrational repair (PIR) [10]
Summary
DNA-dependent protein kinase (DNA-PK) is a heterotrimeric complex that consists of Ku70. One more example of the non-canonical activation of DNA-PKcs has been discovered by studying how example the DNA-PK is involved in HIV-1 post-integrational repair (PIR). One more of thecomplex non-canonical activation of DNA-PKcs has been discovered by studying integration of HIV-1 genome is vital for efficient production of repair new viral how the DNA-PK complex is involved in HIV-1 post-integrational (PIR)particles. We interaction between proteins decreases ofthe infectivity of VSV-G-pseudotyped showed that the phosphorylating activity of DNA-PKcs is crucial for the efficient accomplishment of particles. There are no double-stranded DNA breaks in the product of viral DNA integration In this case, DNA-PK activation is triggered by IN binding to Ku70, since IN mutations disturbing this binding significantly reduce the PIR efficiency and disrupt the pseudovirus sensitivity to Nu7441 [10]. We separately analyzed the literature data on the involvement of the indicated DNA-PK targets in HIV-1 replication
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