Sensitivity and Selectivity of the DNA Damage Sensor Responsible for Activating P53-dependent G1 Arrest

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1996 May 14

PMID 8643488

Citations 106

Authors

L C Huang

K C Clarkin

G M Wahl

Affiliations

Soon will be listed here.

Abstract

The tumor suppressor p53 contributes to maintaining genome stability by inducing a cell cycle arrest or apoptosis in response to conditions that generate DNA damage. Nuclear injection of linearized plasmid DNA, circular DNA with a large gap, or single-stranded circular phagemid is sufficient to induce a p53-dependent arrest. Supercoiled and nicked plasmid DNA, and circular DNA with a small gap were ineffective. Titration experiments indicate that the arrest mechanism in normal human fibroblasts can be activated by very few double strand breaks, and only one may be sufficient. Polymerase chain reaction assays showed that end-joining activity is low in serum-arrested human fibroblasts, and that higher joining activity occurs as cells proceed through G1 or into S phase. We propose that the exquisite sensitivity of the p53-dependent G1 arrest is partly due to inefficient repair of certain types of DNA damage in early G1.

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