Multi-step DNA cleavage in rat liver nuclei is inhibited by thiol reactive agents

Kelvin Cain, Salmaan H. Inayat-Hussain, Ludmilla Kokileva, Gerald M. Cohen

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

DNA fragmentation in isolated rat liver nuclei is a Mg2+-dependent, multi-step process which is potentiated by Ca2+ and cleaves the DNA into ≥700, 200-300 and 30-50 kilobase pair (kbp) fragments, prior to internucleosomal cleavage by Ca2+/Mg2+-dependent endonuclease(s). We now show that Cd2+, Hg2+, dichloroisocoumarin (DCI, a serine protease inhibitor) and N-ethylmaleimide (NEM) block both Mg2+ and Ca2+/Mg2+-dependent processes. Inhibition of DNA cleavage produced an increase in the size of the DNA fragments, from mono-/oligonucleosomes to 30-50, 200-300, ≥700 kbp and finally to intact DNA. NEM and DCI inhibition was blocked by dithiothreitol, and it is proposed that a critical thiol(s) is involved in the DNA cleavage reactions which are a feature of the apoptotic process.

Original languageEnglish
Pages (from-to)255-261
Number of pages7
JournalFEBS Letters
Volume358
Issue number3
DOIs
Publication statusPublished - 30 Jan 1995
Externally publishedYes

Fingerprint

DNA Cleavage
Sulfhydryl Compounds
Liver
Rats
Ethylmaleimide
DNA
Serine Proteinase Inhibitors
Dithiothreitol
Endonucleases
DNA Fragmentation

Keywords

  • Apoptosis
  • Critical thiol
  • Multi-step DNA cleavage

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Genetics
  • Molecular Biology
  • Structural Biology

Cite this

Multi-step DNA cleavage in rat liver nuclei is inhibited by thiol reactive agents. / Cain, Kelvin; Inayat-Hussain, Salmaan H.; Kokileva, Ludmilla; Cohen, Gerald M.

In: FEBS Letters, Vol. 358, No. 3, 30.01.1995, p. 255-261.

Research output: Contribution to journalArticle

Cain, K, Inayat-Hussain, SH, Kokileva, L & Cohen, GM 1995, 'Multi-step DNA cleavage in rat liver nuclei is inhibited by thiol reactive agents', FEBS Letters, vol. 358, no. 3, pp. 255-261. https://doi.org/10.1016/0014-5793(94)01436-5
Cain, Kelvin ; Inayat-Hussain, Salmaan H. ; Kokileva, Ludmilla ; Cohen, Gerald M. / Multi-step DNA cleavage in rat liver nuclei is inhibited by thiol reactive agents. In: FEBS Letters. 1995 ; Vol. 358, No. 3. pp. 255-261.
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