African swine fever virus DEAD-box helicase D1133L promotes OGG1-driven incision of genomic 8-oxoG via HDAC5 deacetylation.

African swine fever virus (ASFV) infection induces oxidative stress and produces oxidative DNA damage bases, including 8-oxoguanine (8-oxoG). It is essential to promptly repair these damages to maintain genome stability. The enzyme 8-oxoguanine DNA glycosylase 1 (OGG1) initiates the base excision repair (BER) pathway by recognizing and incising 8-oxoG and commonly regulates multiple biological processes by interacting with host and viral proteins. In this study, we elucidated the interaction between N-terminal region of ASFV DEAD-box helicase D1133L and OGG1, confirming the unique function of ASFV D1133L in DNA BER. Additionally, we demonstrated for the first time that ASFV D1133L is a substrate for the histone acetyltransferases CBP/p300 in the nucleus, while the deacetylation of D1133L via HDAC5, which primarily takes place in the cytoplasm by interacting with OGG1, markedly enhances the incision activity of OGG1 for 8-oxoG. Taken together, our findings unveil a previously undescribed role of ASFV D1133L in facilitating 8-oxoG incision by binding with OGG1 to safeguard genome integrity.