Processing of bistranded abasic DNA clusters in γ-irradiated human hematopoietic cells
Author
Georgakilas, Alexandros G.; Bennett, Paula V.; Wilson III, David M.; Sutherland, Betsy M.
Abstract
Clustered DNA damages—two or more lesions on opposing strands and within one or two helical turns—are formed in cells by ionizing radiation or radiomimetic antitumordrugs. They are hypothesized to be difficult to repair, and thus are critical biological damages. Since individual abasic sites can be cytotoxic or mutagenic, abasicDNAclusters are likely to have significant cellular impact. Using a novel approach for distinguishing abasic clusters that are very closely spaced (putrescine cleavage) or less closely spaced (Nfo protein cleavage), we measured induction and processing of abasic clusters in 28SC human monocytes that were exposed to ionizing radiation. g-rays induced 1 double-strand break: 1.3 putrescine-detected abasic clusters: 0.8 Nfodetected abasic clusters. After irradiation, the 28SC cells rejoined double-strand breaks efficiently within 24 h. In contrast, in these cells, the levels of abasic clusters decreased very slowly over 14 days to background levels. In vitro repair experiments that used 28SC cell extracts further support the idea of slow processing of specific, closely spaced abasic clusters. Although some clusters were removed by active cellular repair, a substantial number was apparently decreased by ‘splitting’ during DNA replication and subsequent cell division. The existence of abasic clusters in 28SC monocytes, several days after irradiation suggests that they constitute persistent damages that could lead to mutation or cell killing. Originally published in Nucleic Acids Research 2004 Vol. 32, No. 18.
Date
2004
Citation:
APA:
Georgakilas, Alexandros G., & Bennett, Paula V., & Wilson III, David M., & Sutherland, Betsy M.. (January 2004).
Processing of bistranded abasic DNA clusters in γ-irradiated human hematopoietic cells.
Nucleic Acids Research,
32(18),
5609-
5620. Retrieved from
http://hdl.handle.net/10342/3003
MLA:
Georgakilas, Alexandros G., and Bennett, Paula V., and Wilson III, David M., and Sutherland, Betsy M..
"Processing of bistranded abasic DNA clusters in γ-irradiated human hematopoietic cells". Nucleic Acids Research.
32:18. (5609-5620),
January 2004.
September 21, 2023.
http://hdl.handle.net/10342/3003.
Chicago:
Georgakilas, Alexandros G. and Bennett, Paula V. and Wilson III, David M. and Sutherland, Betsy M.,
"Processing of bistranded abasic DNA clusters in γ-irradiated human hematopoietic cells," Nucleic Acids Research 32, no.
18 (January 2004),
http://hdl.handle.net/10342/3003 (accessed
September 21, 2023).
AMA:
Georgakilas, Alexandros G., Bennett, Paula V., Wilson III, David M., Sutherland, Betsy M..
Processing of bistranded abasic DNA clusters in γ-irradiated human hematopoietic cells. Nucleic Acids Research.
January 2004;
32(18):
5609-5620.
http://hdl.handle.net/10342/3003. Accessed
September 21, 2023.
Collections
Publisher
East Carolina University