title: Autophagy promotes DNA-protein crosslink clearance.
abstract: Toxic DNA-protein crosslinks (DPCs) can result from exposure to radiation or chemotherapeutic agents. DPCs can also accumulate during aging or stress. However, the cellular mechanisms underlying clearance of DPCs remain largely unknown. Here, we have identified an important role of autophagy in the processing of DPCs induced by three representative agents: formaldehyde, a chemical used widely in industry; UV light; and camptothecin, a cytotoxic anticancer drug. Autophagy inhibitors, 3-methyladenine (3-MA) or chloroquine (CQ), promoted the accumulation of DPCs in damaged cells and injured organs. siRNA-mediated silencing of Atg5 or Atg7, two essential components for the formation of the autophagosome, gave similar results. In contrast, the autophagy inducer rapamycin (RAP) attenuated DPCs in vitro and in vivo. Our findings reveal the importance of autophagy in controlling the level of DPCs, and may open up a new avenue for understanding the formation and clearance of this detrimental DNA adduct.
authors.affiliation: College of Science, Northwest A&F University, Yangling 712100, Shaanxi, China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Mu
authors.affiliation: College of Science, Northwest A&F University, Yangling 712100, Shaanxi, China.
authors.forename: Qianjin
authors.initials: Q
authors.lastname: Liu
authors.affiliation: College of Science, Northwest A&F University, Yangling 712100, Shaanxi, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Niu
authors.affiliation: College of Science, Northwest A&F University, Yangling 712100, Shaanxi, China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Wang
authors.affiliation: College of Science, Northwest A&F University, Yangling 712100, Shaanxi, China. Electronic address: tangjiang11@nwsuaf.edu.cn.
authors.forename: Jiangjiang
authors.initials: J
authors.lastname: Tang
authors.affiliation: College of Science, Northwest A&F University, Yangling 712100, Shaanxi, China. Electronic address: jduan@nwsuaf.edu.cn.
authors.forename: Jinyou
authors.initials: J
authors.lastname: Duan
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects*; D000071187:Autophagy-Related Protein 5; D000071193:Autophagy-Related Protein 7; D002166:Camptothecin / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002738:Chloroquine / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects*; D005557:Formaldehyde / Q000494:pharmacology; D020868:Gene Silencing; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D020123:Sirolimus / Q000494:pharmacology; D044764:Ubiquitin-Activating Enzymes / Q000235:genetics / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: C502778:ATG5 protein, human; D000970:Antineoplastic Agents; D000071187:Autophagy-Related Protein 5; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; D005557:Formaldehyde; C025946:3-methyladenine; D002738:Chloroquine; C509349:ATG7 protein, human; D000071193:Autophagy-Related Protein 7; D044764:Ubiquitin-Activating Enzymes; D000225:Adenine; D020123:Sirolimus; D002166:Camptothecin
keywords: Autophagy; DNA–protein crosslinks; Formaldehyde