TREX1 acts in degrading damaged DNA from drug-treated tumor cells.
The major mammalian exonuclease TREX1 has been proposed to play a role in DNA repair and drug resistance. However, no cellular evidence substantiates this claim. Recent reports indicate TREX1's involvement in autoimmunity. To further understand its role, we studied TREX1 expression and functionality in anticancer drug-treated tumor cells. We report that the expression and localization of TREX1 are cell-type dependent. Camptothecin and other DNA damaging agents induced both TREX1 protein and its mRNA in a dose- and time-dependent manner. Using a TREX1-inducible cell line, we performed clonogenic assays and found no change in sensitivity of the cells to the agents upon TREX1 induction, suggesting that TREX1 may not play a role in DNA repair or drug sensitivity. Nevertheless, TREX1 serves as a key enzyme in the degradation of DNA from dying cells leading to less cellular DNA. Ubiquitously expressed in normal tissues, TREX1 may act in degrading DNA in all cell types undergoing a dying process before phagocytosis occurs.
Wang
Chuan-Jen
CJ
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA.
Lam
Wing
W
Bussom
Scott
S
Chang
Hua-Mei
HM
Cheng
Yung-Chi
YC
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002166:Camptothecin / Q000494:pharmacology; D045744:Cell Line, Tumor; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects; D005090:Exodeoxyribonucleases / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D010750:Phosphoproteins; D012333:RNA, Messenger; D004247:DNA; D005090:Exodeoxyribonucleases; C429526:three prime repair exonuclease 1; D002166:Camptothecin