Mechanisms of induction of apoptotic DNA fragmentation

N. N. Khodarev, I. A. Sokolova, Andrew T M Vaughan

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Purpose: Despite its common use as an indicator of apoptosis, little is known about the mechanisms controlling apoptotic DNA fragmentation in irradiated cells. This review discusses the pathways of chromatin fragmentation, and the role of both nucleases and chromatin structure in this process. Definitions: DNA fragmentation linked to apoptosis is a combination of cleavage events excising both large DNA fragments within the range 0.4- 1.0 Mbp and 50 kbp followed by random cuts within internucleosomal regions (i.e. DNA laddering). The first two cleavage steps can be detected in virtually all apoptotic cells, but DNA laddering is not ubiquitously observed. Endonucleases that mediate this cleavage of chromatin may be classified by substrate specificity, mode of DNA cleavage and their cofactor requirements. Conclusions: Three major pathways of DNA fragmentation are proposed and discussed: (1) upregulation of endonucleases, (2) their intranuclear/intracellular redistribution and (3) primary changes of chromatin structure.

Original languageEnglish (US)
Pages (from-to)455-467
Number of pages13
JournalInternational Journal of Radiation Biology
Volume73
Issue number5
DOIs
StatePublished - 1998
Externally publishedYes

Fingerprint

DNA fragmentation
DNA Fragmentation
Chromatin
chromatin
induction
fragmentation
DNA
deoxyribonucleic acid
Endonucleases
cleavage
apoptosis
Apoptosis
DNA Cleavage
Cell death
nucleases
substrate specificity
Substrate Specificity
Cells
nuclease
Up-Regulation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology
  • Nuclear Energy and Engineering
  • Radiation

Cite this

Mechanisms of induction of apoptotic DNA fragmentation. / Khodarev, N. N.; Sokolova, I. A.; Vaughan, Andrew T M.

In: International Journal of Radiation Biology, Vol. 73, No. 5, 1998, p. 455-467.

Research output: Contribution to journalArticle

Khodarev, N. N. ; Sokolova, I. A. ; Vaughan, Andrew T M. / Mechanisms of induction of apoptotic DNA fragmentation. In: International Journal of Radiation Biology. 1998 ; Vol. 73, No. 5. pp. 455-467.
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