Activation of the apoptotic endonuclease DFF40 (caspase-activated DNase or nuclease). Oligomerization and direct interaction with histone H1

Xuesong Liu, Hua Zou, Piotr Widlak, William Garrard, Xiaodong Wang

Research output: Contribution to journalArticle

149 Citations (Scopus)

Abstract

DNA fragmentation factor (DFF) is a heterodimeric protein composed of 45-kDa (DFF45) and 40-kDa (DFF40) subunits, a protein that mediates regulated DNA fragmentation and chromatin condensation in response to apoptotic signals. DFF45 is a specific molecular chaperone and an inhibitor for the nuclease activity of DFF40. Previous studies have shown that upon cleavage of DFF45 by caspase-3, the nuclease activity of DFF40 is relieved of inhibition. Here we further investigate the mechanism of DFF40 activation. We demonstrate that DFF45 can also be cleaved and inactivated by caspase-7 but not by caspase-6 and caspase-8. The cleaved DFF45 fragments dissociate from DFF40, allowing DFF40 to oligomerize to form a large functional complex that cleaves DNA by introducing double strand breaks. Histone H1 directly interacts with DFF, confers DNA binding ability to DFF, and stimulates the nuclease activity of DFF40 by increasing its K(cat) and decreasing its K(m).

Original languageEnglish (US)
Pages (from-to)13836-13840
Number of pages5
JournalJournal of Biological Chemistry
Volume274
Issue number20
DOIs
StatePublished - May 14 1999

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Oligomerization
Endonucleases
DNA Fragmentation
Histones
Chemical activation
DNA
3'-nucleotidase
Caspase 6
Caspase 7
Molecular Chaperones
Double-Stranded DNA Breaks
Caspase 8
Protein Subunits
Caspase 3
Chromatin
Cats
caspase-activated deoxyribonuclease
endonuclease P40
Condensation
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Activation of the apoptotic endonuclease DFF40 (caspase-activated DNase or nuclease). Oligomerization and direct interaction with histone H1. / Liu, Xuesong; Zou, Hua; Widlak, Piotr; Garrard, William; Wang, Xiaodong.

In: Journal of Biological Chemistry, Vol. 274, No. 20, 14.05.1999, p. 13836-13840.

Research output: Contribution to journalArticle

Liu, Xuesong ; Zou, Hua ; Widlak, Piotr ; Garrard, William ; Wang, Xiaodong. / Activation of the apoptotic endonuclease DFF40 (caspase-activated DNase or nuclease). Oligomerization and direct interaction with histone H1. In: Journal of Biological Chemistry. 1999 ; Vol. 274, No. 20. pp. 13836-13840.
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