Ys. Yoon et al., POLY(ADP-RIBOSYL)ATION OF HISTONE H1 CORRELATES WITH INTERNUCLEOSOMALDNA FRAGMENTATION DURING APOPTOSIS, The Journal of biological chemistry, 271(15), 1996, pp. 9129-9134
The biochemical role of poly(ADP-ribosyl)ation on internucleosomal DNA
fragmentation associated with apoptosis was investigated in HL 60 hum
an premyelocytic leukemia cells. It was found that UV light and chemot
herapeutic drugs including adriamycin, mitomycin C, and cisplatin incr
eased poly(ADP-ribosyl)ation of nuclear proteins, particularly histone
H1. A poly(ADP-ribose) polymerase inhibitor, 3-aminobenzamide, preven
ted both internucleosomal DNA fragmentation and histone H1 poly(ADP-ri
bosyl)ation in cells treated with the apoptosis inducers, When nuclear
chromatin was made accessible to the exogenous nuclease in a permeabi
lized cell system, chromatin of W-treated cells was more susceptible t
o micrococcal nuclease than the chromatin of control cells. Suppressio
n of histone H1 poly(ADP-ribosyl)ation by 3-aminobenzamide reduced the
micrococcal nuclease digestibility of internucleosomal chromatin in U
V-treated cells, These results suggest that the poly(ADP-ribosyl)ation
of histone H1 correlates with the internucleosomal DNA fragmentation
during apoptosis mediated by DNA damaging agents, This suggestion is s
upported by the finding that xeroderma pigmentosum cells which are def
ective in introducing incision at the site of DNA damage, failed to in
duce DNA fragmentation as well as histone H1 poly(ADP-ribosyl)ation af
ter UV irradiation, We propose that poly(ADP-ribosyl)ation of histone
H1 protein in the early stage of apoptosis facilitates internucleosoma
l DNA fragmentation by increasing the susceptibility of chromatin to c
ellular endonuclease.