DNA fragmentation during apoptosis is caused by frequent single-strand cuts

One of the hallmarks of apoptosis Is the digestion of genomlc DNA by an endonuclease, generating a ladder of small fragments of double-stranded DNA. We have examined the nature of the DNA breaks produced In mouse thymocytes triggered to undergo apoptosis by steroids or by stimulation of the T cell r...

Full description

Saved in:
Bibliographic Details
Published in:Nucleic acids research 1993-09, Vol.21 (18), p.4206-4209
Main Authors: Peitsh, Manuel C., Muüller, Christian, Tschopp, Jü
Format: Article
Language:English
Subjects:
Ageing, cell death
Animals
Apoptosis - drug effects
Apoptosis - genetics
Biological and medical sciences
CD3 Complex - physiology
Cell physiology
Cells, Cultured
Computer Simulation
Dexamethasone - pharmacology
DNA Damage
Electrophoresis, Agar Gel
Fundamental and applied biological sciences. Psychology
Mice
Molecular and cellular biology
Signal Transduction
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:One of the hallmarks of apoptosis Is the digestion of genomlc DNA by an endonuclease, generating a ladder of small fragments of double-stranded DNA. We have examined the nature of the DNA breaks produced In mouse thymocytes triggered to undergo apoptosis by steroids or by stimulation of the T cell receptor. Whereas the typical ladder pattern of ollgonucleosomal fragments was observed after agarose gel electrophoresis, numerous single-strand cuts were detected after electrophoresls under denaturing conditions. Single-strand nicks were found to be very frequent In the internucleosomal regions, but also to occur in the core particle-associated DNA. An Identical pattern of single-strand nicks was obtained when chromatin DNA was exposed to the single-strand cleaving deoxyribonuclease I. The nicked DNA fragments, extracted from apoptotic thymocytes, were sensitive to the action of S1nuclease. We propose that DNA fragmentation Induced during apoptosis is not due to a double-strand cutting enzyme as previously postulated, but rather is the result of single-strand breaks. This ensures the dissociation of the DNA molecule at sites where cuts are found within close proximity.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/21.18.4206