Induction of a novel damage-specific DNA binding protein correlates with enhanced DNA repair in primate cells

Journal Article · Sun Oct 01 00:00:00 EDT 1989 · Molecular Toxicology; (United States)

OSTI ID:5226504

Protic, M; Hirschfeld, S; Tsang, A P; Wagner, M; Dixon, K; Levine, A S ^[1]

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1. Section on Viruses and Cellular Biology, National Institute of Child Health and Human Development, Bethesda, MD (USA)

Pretreatment of mammalian cell with DNA-damaging agents, such as UV light or mitomycin C, but not the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA), results in the enhanced repair of subsequently transfected UV-damaged expression vectors. To determine the cellular factors that are responsible for this enhancement, the authors have used a modified gel retardation assay to detect the proteins that interact with damaged DNA. They have identified a constitutive DNA binding protein in extracts from primate cells that has a high affinity for UV-irradiated double-stranded DNA. Cells pretreated with UV light, mitomycin C, or aphidicolin, but not TPA or serum starvation, have higher levels of this damage-specific DNA binding (DDB) protein. These results suggest that the signal for induction of DDB protein can either be damage to the DNA or interference with cellular DNA replication. The induction of DDB protein varies among primate cells with different phenotypes: (1) virus-transformed repair-proficient cells have partially or fully lost the ability to induce DDB protein above constitutive levels; (2) primary cells from repair-deficient xeroderma pigmentosum (XP) group C, and transformed XP groups A and D, show constitutive DDB protein, but do not show induced levels of this protein 48 h after UV; and (3) primary and transformed repair-deficient cells from one XP E patient are lacking both the constitutive and the induced DDB activity. The correlation between the induction of the DDB protein and the enhanced repair of UV-damaged expression vectors implies the involvement of the DDB protein in this inducible cellular response.

• OSTI ID: 5226504
• Journal Information: Molecular Toxicology; (United States), Vol. 2:4; ISSN 0883-9492
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
DNA REPAIR
PHORBOL ESTERS
BIOLOGICAL EFFECTS
PROTEINS
BIOSYNTHESIS
BLOOD
CULTURE MEDIA
DNA REPLICATION
GENETIC EFFECTS
MITOMYCIN
PHENOTYPE
PLASMIDS
ULTRAVIOLET RADIATION
XP CELLS
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
ANTIMITOTIC DRUGS
ANTINEOPLASTIC DRUGS
BIOLOGICAL MATERIALS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BODY FLUIDS
CARCINOGENS
CELL CONSTITUENTS
DRUGS
ELECTROMAGNETIC RADIATION
ESTERS
MATERIALS
NUCLEIC ACID REPLICATION
ORGANIC COMPOUNDS
RADIATIONS
RECOVERY
REPAIR
SYNTHESIS
560300* - Chemicals Metabolism & Toxicology
560120 - Radiation Effects on Biochemicals
Cells
& Tissue Culture