Synchronous block in DNA synthesis initiation with change in chromatin topology mediated by VP16.

Abstract:

:The impact of chromatin topology on the DNA synthetic process was studied in the human squamous-cell carcinoma cell line SQ-20B. A 1-h exposure < or = 10 microM VP16 produced an increase in DNA supercoil tension, measured by recording laser light scatter from salt-extracted nuclei. This change was precisely paralleled by a decrease in DNA synthesis. The effects on both DNA supercoiling and DNA synthesis were suppressed at VP16 concentrations between 10 and 20 microM. The changes in DNA supercoiling and synthesis at VP16 concentrations -10 microM were eliminated by coincubation with mimosine, a DNA synthesis initiator poison. We conclude that brief exposure to low concentrations of VP16 disturbs the balance of torsional energy within discrete replicon domains by affecting normal topoisomerase II activity at sites of replication initiation. The resultant increase in negative supercoil tension mediates a topologic checkpoint, limiting the initiation of DNA synthesis. Such a checkpoint may be a common pathway for control, both during the normal replicative cycle and subsequent to DNA damage.

journal_name

DNA Cell Biol

journal_title

DNA and cell biology

authors

Narayana A,Khodarev N,Walter S,Vaughan AT

doi

10.1089/dna.1998.17.613

subject

Has Abstract

pub_date

1998-07-01 00:00:00

pages

613-9

issue

7

eissn

1044-5498

issn

1557-7430

journal_volume

17

pub_type

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