Linking RNA polymerase backtracking to genome instability in E. coli.

Abstract:

:Frequent codirectional collisions between the replisome and RNA polymerase (RNAP) are inevitable because the rate of replication is much faster than that of transcription. Here we show that, in E. coli, the outcome of such collisions depends on the productive state of transcription elongation complexes (ECs). Codirectional collisions with backtracked (arrested) ECs lead to DNA double-strand breaks (DSBs), whereas head-on collisions do not. A mechanistic model is proposed to explain backtracking-mediated DSBs. We further show that bacteria employ various strategies to avoid replisome collisions with backtracked RNAP, the most general of which is translation that prevents RNAP backtracking. If translation is abrogated, DSBs are suppressed by elongation factors that either prevent backtracking or reactivate backtracked ECs. Finally, termination factors also contribute to genomic stability by removing arrested ECs. Our results establish RNAP backtracking as the intrinsic hazard to chromosomal integrity and implicate active ribosomes and other anti-backtracking mechanisms in genome maintenance.

journal_name

Cell

journal_title

Cell

authors

Dutta D,Shatalin K,Epshtein V,Gottesman ME,Nudler E

doi

10.1016/j.cell.2011.07.034

subject

Has Abstract

pub_date

2011-08-19 00:00:00

pages

533-43

issue

4

eissn

0092-8674

issn

1097-4172

pii

S0092-8674(11)00848-8

journal_volume

146

pub_type

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