Control of DNA replication in a transformed lymphoid cell line: Coexistence of activator and inhibitor activities

Document Type

Article

Publication Date

1991

Abstract

Proliferating lymphocytes contain an intracellular factor, ADR (activator of DNA replication), which can initiate DNA synthesis in isolated quiescent nuclei. Resting lymphocytes lack ADR activity and contain an intracellular inhibitory factor that suppresses DNA synthesis in normal but not transformed nuclei. In this study we describe a MOLT-4 subline that produces both the activator and inhibitory activities which can be separated by ammonium sulfate fractionation. The inhibitor is heat stable and inhibits ADR-mediated DNA replication in a dose-dependent manner. It does not inhibit DNA polymerase a activity. The inhibitor must be present at the initiation of DNA replication to be effective, as it loses most of its effectiveness if it is added after replication has begun. The presence of inhibitory activity in proliferating MOLT-4 cells, taken with the previous observation that inhibitor derived from normal resting cells does not affect DNA synthesis by MOLT-4 nuclei, suggests that failure of a down-regulating signal may play an important role in proliferative disorder. © 1991.

Publication Title

Cellular immunology

Volume

138

Issue

2

First Page

381

Last Page

389

Comments

This article was published in Cellular immunology, Volume 138, Issue 2, Pages 381-389.

The published version is available at http://dx.doi.org/10.1016/0008-8749(91)90162-5.

Copyright © 1991.

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