scholarly journals Separate DNA Pol II- and Pol IV-Dependent Pathways of Stress-Induced Mutation during Double-Strand-Break Repair in Escherichia coli Are Controlled by RpoS

2010 ◽  
Vol 192 (18) ◽  
pp. 4694-4700 ◽  
Author(s):  
Ryan L. Frisch ◽  
Yang Su ◽  
P. C. Thornton ◽  
Janet L. Gibson ◽  
Susan M. Rosenberg ◽  
...  

ABSTRACT Previous work showed that about 85% of stress-induced mutations associated with DNA double-strand break repair in carbon-starved Escherichia coli result from error-prone DNA polymerase IV (Pol IV) (DinB) and that the mutagenesis is controlled by the RpoS stress response, which upregulates dinB. We report that the remaining mutagenesis requires high-fidelity Pol II, and that this component also requires RpoS. The results identify a second DNA polymerase contributing to stress-induced mutagenesis and show that RpoS promotes mutagenesis by more than the simple upregulation of dinB.

PLoS Genetics ◽  
2020 ◽  
Vol 16 (1) ◽  
pp. e1008473 ◽  
Author(s):  
Martin A. White ◽  
Elise Darmon ◽  
Manuel A. Lopez-Vernaza ◽  
David R. F. Leach

2020 ◽  
Vol 48 (15) ◽  
pp. 8490-8508 ◽  
Author(s):  
Sarah S Henrikus ◽  
Camille Henry ◽  
Amy E McGrath ◽  
Slobodan Jergic ◽  
John P McDonald ◽  
...  

Abstract Several functions have been proposed for the Escherichia coli DNA polymerase IV (pol IV). Although much research has focused on a potential role for pol IV in assisting pol III replisomes in the bypass of lesions, pol IV is rarely found at the replication fork in vivo. Pol IV is expressed at increased levels in E. coli cells exposed to exogenous DNA damaging agents, including many commonly used antibiotics. Here we present live-cell single-molecule microscopy measurements indicating that double-strand breaks induced by antibiotics strongly stimulate pol IV activity. Exposure to the antibiotics ciprofloxacin and trimethoprim leads to the formation of double strand breaks in E. coli cells. RecA and pol IV foci increase after treatment and exhibit strong colocalization. The induction of the SOS response, the appearance of RecA foci, the appearance of pol IV foci and RecA-pol IV colocalization are all dependent on RecB function. The positioning of pol IV foci likely reflects a physical interaction with the RecA* nucleoprotein filaments that has been detected previously in vitro. Our observations provide an in vivo substantiation of a direct role for pol IV in double strand break repair in cells treated with double strand break-inducing antibiotics.


2020 ◽  
Vol 21 (12) ◽  
pp. 4245
Author(s):  
Tuyen T. Dang ◽  
Julio C. Morales

Cellular survival is dependent on the efficient replication and transmission of genomic information. DNA damage can be introduced into the genome by several different methods, one being the act of DNA replication. Replication is a potent source of DNA damage and genomic instability, especially through the formation of DNA double strand breaks (DSBs). DNA polymerase alpha is responsible for replication initiation. One subunit of the DNA polymerase alpha replication machinery is POLA2. Given the connection between replication and genomic instability, we decided to examine the role of POLA2 in DSB repair, as little is known about this topic. We found that loss of POLA2 leads to an increase in spontaneous DSB formation. Loss of POLA2 also slows DSB repair kinetics after treatment with etoposide and inhibits both of the major double strand break repair pathways: non-homologous end-joining and homologous recombination. In addition, loss of POLA2 leads to increased sensitivity to ionizing radiation and PARP1 inhibition. Lastly, POLA2 expression is elevated in glioblastoma multiforme tumors and correlates with poor overall patient survival. These data demonstrate a role for POLA2 in DSB repair and resistance to genotoxic stress.


DNA Repair ◽  
2009 ◽  
Vol 8 (12) ◽  
pp. 1434-1443 ◽  
Author(s):  
Jane I. Grove ◽  
Stuart R. Wood ◽  
Geoffrey S. Briggs ◽  
Neil J. Oldham ◽  
Robert G. Lloyd

PLoS Genetics ◽  
2009 ◽  
Vol 5 (2) ◽  
pp. e1000389 ◽  
Author(s):  
Daniel Lucas ◽  
Beatriz Escudero ◽  
José Manuel Ligos ◽  
Jose Carlos Segovia ◽  
Juan Camilo Estrada ◽  
...  

2015 ◽  
Vol 95 (5) ◽  
pp. 754-768 ◽  
Author(s):  
Stefanie H. Chen ◽  
Rose T. Byrne ◽  
Elizabeth A. Wood ◽  
Michael M. Cox

Sign in / Sign up

Export Citation Format

Share Document