A novel DNA damage-inducible transcript, gadd7, inhibits cell growth, but lacks a protein product.
gadd7 cDNA was isolated from Chinese hamster ovary (CHO) cells on the basis of increased levels of RNA following treatment with UV radiation. The transcript for gadd7, as well as for four other gadd genes, was found to increase rapidly and coordinately following several different types of DNA damage and more slowly following other stresses that elicit growth arrest. Agents that induce gadd7 RNA include alkylating agents, such as methyl methanesulfonate (MMS), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and mechlorethamine HCl (HN2), oxidizing agents, such as hydrogen peroxide, and growth arrest signals, such as medium depletion (starvation). Since growth arrest is a cellular consequence of many types of DNA damage in normal cells, it was thought that gadd7 may play a role in the cellular response to DNA damage. Indeed, overexpression of gadd7 led to a decrease in cell growth. Interestingly, gadd7 cDNA does not contain an appreciable open reading frame and does not appear to encode a protein product, but instead may function at the RNA level.
Hollander
M C
MC
Laboratory of Molecular Pharmacology, Division of Basic Science, National Cancer Institute, Bethesda, MD 20892, USA.
Alamo
I
I
Fornace
A J
AJ
D000477:Alkylating Agents / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002455:Cell Division / Q000502:physiology*; D002460:Cell Line; D003001:Cloning, Molecular; D006224:Cricetinae; D003470:Culture Media; D004249:DNA Damage; D018076:DNA, Complementary / Q000235:genetics; D018628:Gene Dosage; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008647:Mesocricetus; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000235:genetics; D016877:Oxidants / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D014407:Tumor Cells, Cultured
D000477:Alkylating Agents; D003470:Culture Media; D018076:DNA, Complementary; D016877:Oxidants; D012333:RNA, Messenger; D008741:Methyl Methanesulfonate; D006861:Hydrogen Peroxide