Human apurinic/apyrimidinic endonuclease (Ape1) and its N-terminal truncated form (AN34) are involved in DNA fragmentation during apoptosis

Akira Yoshida, Yoshimasa Urasaki, Mark Waltham, Ann Charlotte Bergman, Philippe Pourquier, Dominic G. Rothwell, Manabu Inuzuka, John N. Weinstein, Takanori Ueda, Ettore Appella, Ian D. Hickson, Yves Pommier

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41 Citations (Scopus)

Abstract

We previously isolated a 34-kDa nuclease (AN34) from apoptotic human leukemia cells. Here, we identify AN34 as an N-terminally truncated form of human AP endonuclease (Ape1) lacking residues 1-35 (Δ35-Ape1). Although Ape1 has hitherto been considered specific for damaged DNA (specific to AP site), recombinant AN34 (Δ35-Ape1) possesses significant endonuclease activity on undamaged (normal) DNA and in chromatin. AN34 also displays enhanced 3′-5′ exonuclease activity. Caspase-3 activates AN34 in a cell-free system, although caspase-3 cannot cleave Ape1 directly in vitro. We also found that Ape1 itself preferentially cleaves damaged chromatin DNA isolated from cells treated with apoptotic stimuli and that silencing of Ape1 expression decreases apoptotic DNA fragmentation in DFF40/CAD-deficient cells. Thus, we propose that AN34 and Ape1 participate in the process of chromatin fragmentation during apoptosis.

Original languageEnglish
Pages (from-to)37768-37776
Number of pages9
JournalThe Journal of Biological Chemistry
Volume278
Issue number39
DOIs
Publication statusPublished - 26 Sep 2003
Externally publishedYes

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