The novel gene LRP15 is regulated by DNA methylation and confers increased efficiency of DNA repair of ultraviolet-induced DNA damage.
LRP15 is a novel gene cloned from lymphocytic cells, and its function is still unknown. Bioinformatic data showed that LRP15 might be regulated by DNA methylation and had an important role in DNA repair. In this study, we investigate whether the expression of LRP15 is regulated by DNA methylation, and whether overexpression of LRP15 increases efficiency of DNA repair of UV-induced DNA damage in HeLa cells. The results showed (1) the promoter of LRP15 was hypermethylated in HeLa cells, resulting a silence of its expression. Gene expression was restored by a demethylating agent, 5-aza-2'-deoxycytidine, but not by a histone deacetylase inhibitor, trichostatin A; (2) overexpression of LRP15 inhibited HeLa cell proliferation, and the numbers of cells in the G2/M phase of the cell cycle in cells transfected with LRP15 increased about 10% compared with controls; (3) cyclin B1 level was much lower in cells overexpressing LRP15 than in control cells; and (4) after exposure to UV radiation, the LRP15-positive cells showed shorter comet tails compared with the LRP15-negative cells. From these results we conclude that the expression of LRP15 is controlled by methylation in its promoter in HeLa cells, and LRP15 confers resistance to UV damage and accelerates the DNA repair rate.
Xu
Zhou-Min
ZM
Department of Oncology, Shanghai Corps Hospital, Chinese People's Armed Police Forces, Shanghai 201103, China. xuzhoumin@yahoo.com.cn
Gao
Wei-Ran
WR
Mei
Qi
Q
Chen
Jian
J
Lu
Jing
J
D000818:Animals; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001483:Base Sequence; D019556:COS Cells; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002522:Chlorocebus aethiops; D020552:Comet Assay; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D004249:DNA Damage; D019175:DNA Methylation / Q000187:drug effects / Q000528:radiation effects*; D004260:DNA Repair / Q000187:drug effects / Q000528:radiation effects*; D000077209:Decitabine; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D006367:HeLa Cells; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014466:Ultraviolet Rays
C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D006877:Hydroxamic Acids; C477813:LRRC3B protein, human; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C012589:trichostatin A; D000077209:Decitabine; D001374:Azacitidine