TY - JOUR

T1 - Bacterial Chromosome Replication and DNA Repair During the Stringent Response

AU - Sinha, Anurag Kumar

AU - Løbner-Olesen, Anders

AU - Riber, Leise

PY - 2020

Y1 - 2020

N2 - The stringent response regulates bacterial growth rate and is important for cell survival under changing environmental conditions. The effect of the stringent response is pleiotropic, affecting almost all biological processes in the cell including transcriptional downregulation of genes involved in stable RNA synthesis, DNA replication, and metabolic pathways, as well as the upregulation of stress-related genes. In this Review, we discuss how the stringent response affects chromosome replication and DNA repair activities in bacteria. Importantly, we address how accumulation of (p)ppGpp during the stringent response shuts down chromosome replication using highly different strategies in the evolutionary distant Gram-negativeEscherichia coliand Gram-positiveBacillus subtilis.Interestingly, (p)ppGpp-mediated replication inhibition occurs downstream of the origin inB. subtilis, whereas replication inhibition inE. colitakes place at the initiation level, suggesting that stringent cell cycle arrest acts at different phases of the replication cycle betweenE. coliandB. subtilis. Furthermore, we address the role of (p)ppGpp in facilitating DNA repair activities and cell survival during exposure to UV and other DNA damaging agents. In particular, (p)ppGpp seems to stimulate the efficiency of nucleotide excision repair (NER)-dependent repair of DNA lesions. Finally, we discuss whether (p)ppGpp-mediated cell survival during DNA damage is related to the ability of (p)ppGpp accumulation to inhibit chromosome replication.

AB - The stringent response regulates bacterial growth rate and is important for cell survival under changing environmental conditions. The effect of the stringent response is pleiotropic, affecting almost all biological processes in the cell including transcriptional downregulation of genes involved in stable RNA synthesis, DNA replication, and metabolic pathways, as well as the upregulation of stress-related genes. In this Review, we discuss how the stringent response affects chromosome replication and DNA repair activities in bacteria. Importantly, we address how accumulation of (p)ppGpp during the stringent response shuts down chromosome replication using highly different strategies in the evolutionary distant Gram-negativeEscherichia coliand Gram-positiveBacillus subtilis.Interestingly, (p)ppGpp-mediated replication inhibition occurs downstream of the origin inB. subtilis, whereas replication inhibition inE. colitakes place at the initiation level, suggesting that stringent cell cycle arrest acts at different phases of the replication cycle betweenE. coliandB. subtilis. Furthermore, we address the role of (p)ppGpp in facilitating DNA repair activities and cell survival during exposure to UV and other DNA damaging agents. In particular, (p)ppGpp seems to stimulate the efficiency of nucleotide excision repair (NER)-dependent repair of DNA lesions. Finally, we discuss whether (p)ppGpp-mediated cell survival during DNA damage is related to the ability of (p)ppGpp accumulation to inhibit chromosome replication.

KW - (p)ppGpp

KW - DNA replication

KW - DNA repair

KW - stringent response

KW - genome stability

KW - Escherichia coli

KW - Bacillus subtilis

KW - NUCLEOTIDE EXCISION-REPAIR

KW - ESCHERICHIA-COLI

KW - BACILLUS-SUBTILIS

KW - RNA-POLYMERASE

KW - MIOC TRANSCRIPTION

KW - GROWTH-RATE

KW - CELL CYCLE

KW - PPGPP

KW - (P)PPGPP

KW - INITIATION

U2 - 10.3389/fmicb.2020.582113

DO - 10.3389/fmicb.2020.582113

M3 - Review

C2 - 32983079

VL - 11

JO - Frontiers in Microbiology

JF - Frontiers in Microbiology

SN - 1664-302X

M1 - 582113

ER -