Single-strand Interruptions in Replicating Chromosomes Cause Double-strand Breaks

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2001 Jul 19

PMID 11459959

Citations 186

Authors

A Kuzminov

Affiliations

Soon will be listed here.

Abstract

Replication-dependent chromosomal breakage suggests that replication forks occasionally run into nicks in template DNA and collapse, generating double-strand ends. To model replication fork collapse in vivo, I constructed phage lambda chromosomes carrying the nicking site of M13 bacteriophage and infected with these substrates Escherichia coli cells, producing M13 nicking enzyme. I detected double-strand breaks at the nicking sites in lambda DNA purified from these cells. The double-strand breakage depends on (i) the presence of the nicking site; (ii) the production of the nicking enzyme; and (iii) replication of the nick-containing chromosome. Replication fork collapse at nicks in template DNA explains diverse phenomena, including eukaryotic cell killing by DNA topoisomerase inhibitors and inviability of recombination-deficient vertebrate cell lines.

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