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Title: 2',3'-dideoxythymidine 5'-triphosphate inhibition of DNA replication and ultraviolet-induced DNA repair synthesis in human cells: evidence for involvement of DNA polymerase delta

Journal Article · · Biochemistry; (United States)
DOI:https://doi.org/10.1021/bi00384a002· OSTI ID:5874558

It is well established that DNA replication and ultraviolet-induced DNA repair synthesis in mammalian cells are aphidicolin-sensitive and thus are mediated by one or both of the aphidicolin-sensitive DNA polymerases, ..cap alpha.. and/or delta. Recently, it has been shown that DNA polymerase delta is much more sensitive to inhibition by the nucleotide analogue 2',3'-dideoxythymidine 5'-triphosphate (ddTTP) than DNA polymerase ..cap alpha.. but is less sensitive than DNA polymerase BETA. The authors find that DNA replication and ultraviolet-induced DNA repair synthesis in permeable human fibroblasts are also more sensitive to inhibition by ddTTP than polymerase ..cap alpha.. and less sensitive than polymerase ..beta... The K/sub i/ for ddTTP of replication is about 40 ..mu..M and that of repair synthesis is about 25 ..mu..M. These are both much less than the K/sub i/ of polymerase ..cap alpha.. (which is greater than 200 ..mu..M but greater than the K/sub i/ of polymerase ..beta.. (which is less than 2 ..mu..M). These data suggest that DNA polymerase delta participates in DNA replication and ultraviolet-induced DNA repair synthesis in human cells.

Research Organization:
Washington Univ. School of Medicine, St. Louis, MO
OSTI ID:
5874558
Journal Information:
Biochemistry; (United States), Vol. 26:10
Country of Publication:
United States
Language:
English