Association between DNA cleavage during apoptosis and regions of chromatin replication

Nikolai N. Khodarev, Irina A. Sokolova, Andrew T M Vaughan

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

We have addressed the association between the site of DNA cleavage during apoptosis and DNA replication. DNA double strand breaks were introduced into chromatin containing pulse labeled nascent DNA by the induction of apoptosis or autocleavage of isolated nuclei. The location of these breaks in relation to nascent DNA were revealed by Bal 31 exonuclease digestion at the cut sites. Our data show that Bal31 accessible cut sites are directly linked to regions enriched in nascent DNA. We suggest that these regions coincide with the termini of replication domains, possibly linked by strong DNA-matrix interactions with biophysically defined topological structures of 0.5 1.3 Mbp in size. The 50 kbp fragments that are commonly observed as products of apoptosis are also enriched in nascent DNA within internal regions but not at their termini. It is proposed that these fragments contain a subset of replicon DNA that is excised during apoptosis through recognition of their weak attachment to the nuclear matrix within the replication domain.

Original languageEnglish (US)
Pages (from-to)604-615
Number of pages12
JournalJournal of Cellular Biochemistry
Volume70
Issue number4
DOIs
StatePublished - Sep 15 1998
Externally publishedYes

Keywords

  • Apoptosis
  • Bal 31
  • DNA cleavage
  • DNA replication
  • Endonuclease
  • Topological domains

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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