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Role of ATP in UV-induced DNA excision repair in human cells

Journal Article · · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:7187861
In permeable human fibroblasts, UV-induced DNA excision repair is dependent on ATP, with a K/sub m/ of approximately 1 mM. Omission of ATP from the reaction mix completely inhibits damage-specific incision of DNA, but has little effect on repair patch synthesis proceeding from previously incised sites. UV-induced excision repair in permeable xeroderma pigmentosum (XP) cells complemented with T4 UV endonuclease is also totally dependent on ATP. Because the T4 enzyme is not ATP-dependent, ATP must be required for an endogenous activity other than the incision of damaged DNA. Alkaline elution reveals that, in the absence of ATP, T4 UV endonuclease does incise the DNA of permeable UV-irradiated XP cells, but that the incision rate is stimulated approximately 2-fold by the addition of ATP. This 2-fold stimulation of incision can not, however, be responsible for the absolute ATP dependence of excision repair in UV endonuclease-complemented XP cells. Apparently, although T4 UV endonuclease can incise damaged nuclear DNA in the absence of ATP, the incised sites must also be altered in an ATP-dependent reaction before subsequent steps of the repair process can proceed. This conclusion, coupled with the fact that ATP stimulates incision of damaged nuclear DNA by T4 UV endonuclease and is absolutely required for incision of damaged nuclear DNA by the endogenous human UV endonuclease, suggests that an important function of the early ATP-dependent step in UV-induced excision repair is to make damaged sites in DNA accessible to repair enzymes.
Research Organization:
Washington Univ., St. Louis, MO
OSTI ID:
7187861
Report Number(s):
CONF-8606151-
Journal Information:
Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:6; ISSN FEPRA
Country of Publication:
United States
Language:
English

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Related Subjects

560120* -- Radiation Effects on Biochemicals
Cells
& Tissue Culture
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
ATP
BACTERIOPHAGES
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CONNECTIVE TISSUE CELLS
DISEASES
DNA
DNA REPAIR
DNA-ASE
ELECTROMAGNETIC RADIATION
ENDONUCLEASES
ENZYME ACTIVITY
ENZYMES
ESTERASES
FIBROBLASTS
GENETIC EFFECTS
GENETIC RADIATION EFFECTS
HYDROLASES
MAMMALS
MAN
MICROORGANISMS
NUCLEIC ACIDS
NUCLEOTIDES
ORGANIC COMPOUNDS
PARASITES
PHOSPHODIESTERASES
PRIMATES
RADIATION EFFECTS
RADIATIONS
RECOVERY
REPAIR
SKIN DISEASES
SOMATIC CELLS
ULTRAVIOLET RADIATION
VERTEBRATES
VIRUSES
XERODERMA PIGMENTOSUM
XP CELLS