Insight into the interaction between PriB and DnaT on bacterial DNA replication restart: Significance of the residues on PriB dimer interface and highly acidic region on DnaT

2019 ◽  
Vol 1867 (4) ◽  
pp. 367-375 ◽  
Author(s):  
Saki Fujiyama ◽  
Yoshito Abe ◽  
Mitsunori Shiroishi ◽  
Yohei Ikeda ◽  
Tadashi Ueda
2017 ◽  
Vol 46 (2) ◽  
pp. 504-519 ◽  
Author(s):  
Tricia A Windgassen ◽  
Sarah R Wessel ◽  
Basudeb Bhattacharyya ◽  
James L Keck

1982 ◽  
Vol 187 (3) ◽  
pp. 501-509 ◽  
Author(s):  
Lee Rowen ◽  
Joan A. Kobori ◽  
Stewart Scherer

2016 ◽  
Vol 9 (412) ◽  
pp. ra11-ra11 ◽  
Author(s):  
Canhua Lu ◽  
Ernesto S. Nakayasu ◽  
Li-Qun Zhang ◽  
Zhao-Qing Luo

2018 ◽  
Vol 43 ◽  
pp. 38-45 ◽  
Author(s):  
Yilai Li ◽  
Jeremy W Schroeder ◽  
Lyle A Simmons ◽  
Julie S Biteen

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Sunetra Roy ◽  
Karl-Heinz Tomaszowski ◽  
Jessica W Luzwick ◽  
Soyoung Park ◽  
Jun Li ◽  
...  

Classically, p53 tumor suppressor acts in transcription, apoptosis, and cell cycle arrest. Yet, replication-mediated genomic instability is integral to oncogenesis, and p53 mutations promote tumor progression and drug-resistance. By delineating human and murine separation-of-function p53 alleles, we find that p53 null and gain-of-function (GOF) mutations exhibit defects in restart of stalled or damaged DNA replication forks that drive genomic instability, which isgenetically separable from transcription activation. By assaying protein-DNA fork interactions in single cells, we unveil a p53-MLL3-enabled recruitment of MRE11 DNA replication restart nuclease. Importantly, p53 defects or depletion unexpectedly allow mutagenic RAD52 and POLθ pathways to hijack stalled forks, which we find reflected in p53 defective breast-cancer patient COSMIC mutational signatures. These data uncover p53 as a keystone regulator of replication homeostasis within a DNA restart network. Mechanistically, this has important implications for development of resistance in cancer therapy. Combined, these results define an unexpected role for p53-mediated suppression of replication genome instability.


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