AI Article Synopsis
- FEN1 is suggested to be essential for the long patch base excision repair (LP-BER) subpathway, based on in vitro studies.
- FEN1-deficient DT40 chicken cells show increased sensitivity to hydrogen peroxide (H2O2), indicating a deficiency in BER that affects cell survival.
- Experiments demonstrate that while FEN1 null cells are deficient in LP-BER activity, they retain normal function in single-nucleotide BER, highlighting FEN1's specific role in processing flap-containing intermediates during DNA repair.
Article Abstract
From in vitro studies, flap endonuclease 1 (FEN1) has been proposed to play a role in the long patch (LP) base excision repair (BER) subpathway. Yet the role of FEN1 in BER in the context of the living vertebrate cell has not been thoroughly explored. In the present study, we cloned a DT40 chicken cell line with a deletion in the FEN1 gene and found that these FEN1-deficient cells exhibited hypersensitivity to H(2)O(2). This oxidant produces genotoxic lesions that are repaired by BER, suggesting that the cells have a deficiency in BER affecting survival. In experiments with extracts from the isogenic FEN1 null and wild-type cell lines, the LP-BER activity of FEN1 null cells was deficient, whereas repair by the single-nucleotide BER subpathway was normal. Other consequences of the FEN1 deficiency were also evaluated. These results illustrate that FEN1 plays a role in LP-BER in higher eukaryotes, presumably by processing the flap-containing intermediates of BER.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2824787 | PMC |
| http://dx.doi.org/10.1158/1541-7786.MCR-09-0253 | DOI Listing |
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