摘要
African swine fever virus(ASFV)infection induces oxidative stress and produces oxidative DNA damage bases,leading to oxidative DNA base damage,including the formation of 8-oxoguanine(8-oxoG).Prompt repair of these lesions is essential 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,while also regulating multiple biological processes through interactions with host and viral proteins.In this study,we identified a specific interaction between the N-terminal region of ASFV DEAD-box helicase D1133L and OGG1,establishing a unique role for ASFV D1133L in DNA BER.Furthermore,we demonstrated for the first time that ASFV D1133L is a substrate for the histone acetyltransferases CBP/p300 in the nucleus.Conversely,deacetylation of D1133L by HDAC5,which predominantly occurs in the cytoplasm through its interaction with OGG1,markedly enhances OGG1 incision activity on 8-oxoG.Taken together,our findings reveal a previously unrecognized function of ASFV D1133L in promoting 8-oxoG repair by binding to OGG1 to safeguard genome integrity.
基金
supported by grants from the National Natural Science Foundation of China(U24A20450 and 32072830)
the National Key Research and Development Program(2021YFD1800101)
Gansu Provincial Major Project for Science and Technology Development(22ZD6NA001)
Fundamental Research Funds for the Central Universities(31920230184)
the Key Program of Natural Science Foundation of Gansu(24JRRA011)
the Science Fund for Creative Research Groups of Gansu Province(22jR5RA024)
Special Project of Gansu Province(22CX8NA011)
the Central Public-interest Scientific Institution Basal Research Fund(CAAS-ZDRW202409)
the National Agricultural Science and Technology Innovation Program(CAAS-ASTIP-2021-LVRI).
