DNA Damage-Induced Replication Fork Regression and Processing in
            <i>Escherichia coli</i>

Courcelle, Justin; Donaldson, Janet R.; Chow, Kin-Hoe; Courcelle, Charmain T.

doi:10.1126/science.1081328

Cited by 229 publications

(291 citation statements)

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“…Plasmid stability, genomic and plasmid DNA extractions, Southern analysis, density-labeled CsCl analysis, and DNA accumulation assays have been described previously (29,31,46). Detailed descriptions can be found in SI Materials and Methods.…”

Section: Methodsmentioning

confidence: 99%

Completion of DNA replication in Escherichia coli

Wendel

Courcelle

2014

Proc. Natl. Acad. Sci. U.S.A.

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134

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The mechanism by which cells recognize and complete replicated regions at their precise doubling point must be remarkably efficient, occurring thousands of times per cell division along the chromosomes of humans. However, this process remains poorly understood. Here we show that, in Escherichia coli, the completion of replication involves an enzymatic system that effectively counts pairs and limits cellular replication to its doubling point by allowing converging replication forks to transiently continue through the doubling point before the excess, over-replicated regions are incised, resected, and joined. Completion requires RecBCD and involves several proteins associated with repairing double-strand breaks including, ExoI, SbcDC, and RecG. However, unlike double-strand break repair, completion occurs independently of homologous recombination and RecA. In some bacterial viruses, the completion mechanism is specifically targeted for inactivation to allow over-replication to occur during lytic replication. The results suggest that a primary cause of genomic instabilities in many double-strand-break-repair mutants arises from an impaired ability to complete replication, independent from DNA damage.replication completion | double-strand break repair | RecBCD | homologous recombination | SbcDC

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Section: Methodsmentioning

confidence: 99%

Completion of DNA replication in Escherichia coli

Wendel

Courcelle

2014

Proc. Natl. Acad. Sci. U.S.A.

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134

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“…1 and 2). In E. coli, RecQ and RecJ degrade the nascent lagging strand at UV-induced stalled DNA replication forks to promote fork stabilization and suppress inappropriate recombination (29). In yeast, Sgs1 is required for stabilization of stalled replication forks induced by hydroxyurea treatment (30).…”

Section: Roles In Dna Replicationmentioning

confidence: 99%

Junction of RecQ Helicase Biochemistry and Human Disease

Opresko

Cheng

Bohr

2004

Journal of Biological Chemistry

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RecQ helicases are a family of conserved enzymes required for maintaining the genomic integrity, that function as suppressors of inappropriate recombination. Mutations in Escherichia coli RecQ and in the Saccharomyces cerevisiae RecQ homolog, Sgs1, result in an increased frequency of illegitimate recombination (1). In humans, defects in three RecQ family proteins are associated with rare autosomal-recessive disorders characterized by genomic instability and increased cancer susceptibility. Mutations in WRN, BLM, and RECQ4 give rise to the disorders Werner syndrome (WS), 1 Bloom syndrome (BS), and Rothmund-Thomson syndrome (RTS), respectively, the clinical features of which have been reviewed elsewhere (2). Briefly, BS patients are predisposed to many types of cancer with the mean age of onset of 24. WS patients are especially predisposed to sarcomas, premature aging, and ageassociated diseases. RTS patients have a characteristic rash, poikiloderma, and are predisposed to osteosarcomas and some features of premature aging. The molecular basis of genomic instability and premature aging is not well understood.The RecQ family is named after E. coli RecQ helicase, a well characterized prototypical member (Fig. 1). Helicases separate complementary strands of nucleic acids in a reaction coupled to NTP hydrolysis. RecQ helicases have a common helicase domain, which binds and hydrolyzes ATP. Most RecQ helicases have a highly conserved multifunctional RecQ C-terminal region (RQC) and a helicase RNase D C-terminal (HRDC) domain (Fig. 1). A recent report of the x-ray crystal structure for the E. coli RecQ catalytic core indicates that the RQC domain contains DNA and protein binding motifs (3). Consistent with this, the RQC domain of WRN binds to various DNA substrates and mediates interactions with other proteins involved in DNA metabolism (4). The E. coli RecQ HRDC domain is required for stable DNA binding but not for catalytic activity (5). Similarly, the HRDC domain of human WRN also binds DNA substrates but is not required for catalytic activity (4). Two RecQ family proteins WRN and Xenopus laevis FFA-1 also have an exonuclease domain. Bacteria and yeast have a single RecQ family member, and up to five RecQ members have been found in mammals.To better define the precise roles of RecQ helicases in vivo, significant research effort has been devoted to characterizing the biochemical properties of RecQ helicases and to identifying important protein interactions between RecQ helicases and other well characterized proteins. This review will focus primarily on these aspects and on the most well characterized RecQ helicases, due to space limitations. RecQ helicase genetic studies in yeast have been recently reviewed elsewhere (6). Biochemical Characteristics of RecQ HelicasesAll RecQ helicases purified and characterized to date unwind duplex DNA in a 3Ј to 5Ј direction with respect to the DNA strand bound by the helicase. Substrate preferences are determined by comparing product amounts, reaction kinetics, and/or protein affini...

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“…RuvAB-catalyzed RFR has been invoked in the rescue of replication forks stalled by either denaturation of temperature-sensitive components of the DNA polymerase III holoenzyme (Pol III HE), the cellular replicase (23) (the ␣ and subunits (24)), or in mutants lacking the Rep DNA helicase (24), which causes slower replication fork progression (25) because of reduced ability to clear proteins from in front of the replication fork (26). RecG-catalyzed fork regression has been suggested to occur in UV-irradiated cells after replication forks stall, primarily because they encounter an RNA polymerase that has stalled at a leading-strand cyclopyrimidine dimer (CPD) (27,28), whereas RecA-catalyzed regression is proposed to occur after stalling forks by denaturation of a thermosensitive replication fork DNA helicase, DnaB (29,30), and also possibly after UV irradiation (31).…”

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confidence: 99%