Post-Integrational DNA Repair of HIV-1 Is Associated with Activation of the DNA-PK and ATM Cellular Protein Kinases and Phosphorylation of Their Targets

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Andrey N. Anisenko^1,2,3,a*, Anastasiia A. Nefedova³, Igor I. Kireev², Marina B. Gottikh^1,2

¹Chemistry Department, Lomonosov Moscow State University, 119991 Moscow, Russia

²Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia

³Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119991 Moscow, Russia

^* To whom correspondence should be addressed.

Received: March 28, 2024; Revised: April 18, 2024; Accepted: April 25, 2024

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Integration of the DNA copy of HIV-1 genome into the cellular genome results in series of damages, repair of which is critical for successful replication of the virus. We have previously demonstrated that the ATM and DNA-PK kinases, normally responsible for repairing double-strand breaks in the cellular DNA, are required to initiate the HIV-1 DNA postintegrational repair, even though integration does not result in DNA double-strand breaks. In this study, we analyzed changes in phosphorylation status of ATM (pSer1981), DNA-PK (pSer2056), and their related kinase ATR (pSer428), as well as their targets: Chk1 (pSer345), Chk2 (pThr68), H2AX (pSer139), and p53 (pSer15) during the HIV-1 DNA postintegrational repair. We have shown that ATM and DNA-PK, but not ATR, undergo autophosphorylation during postintegrational DNA repair and phosphorylate their target proteins Chk2 and H2AX. These data indicate common signaling mechanisms between the double-strand DNA break repair and postintegrational repair of HIV-1 DNA.

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KEY WORDS: HIV-1, DNA-PK, ATM, kinases, DNA repair, post-integrational DNA repair

DOI: 10.1134/S0006297924060117

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