RecA protein promotes the regression of stalled replication forks
            <i>in vitro</i>

Robu, Mara E.; Inman, Ross B.; Cox, Michael M.

doi:10.1073/pnas.131022698

Cited by 149 publications

(125 citation statements)

References 48 publications

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“…In addition, RecA* stimulates the cleavage of the regulatory subunit UmuD to form a fully functional PolV (UmuD' 2 -UmuC) [12,13], and the RecA-ssDNA filaments are required for both homologous recombination and TLS [14]. This ssDNA-binding activity of RecA has been suggested to induce fork regression forming a chicken-foot structure, or to act as a primer for TLS allowing DDT and replication restart [15], as illustrated in Figure 1.…”

Section: Ddt In Prokaryotesmentioning

confidence: 99%

“…Template switching involves homologous sister chromatid invasion/cohesion, high-fidelity DNA synthesis and the subsequent resolution of a Holliday junction ( Figure 1). Fork regression (Figure 1) is thought to operate much as it does in bacteria, requiring ssDNA binding protein and RecA to produce a characteristic chicken-foot structure [15]. Experimental evidence to support a chicken-foot structure in eukaryotes came from a recent report [136] that yeast Rad5 has a DNA helicase activity that facilitates replication fork regression.…”

Section: Error-free Ddtmentioning

confidence: 99%

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Eukaryotic DNA damage tolerance and translesion synthesis through covalent modifications of PCNA

Andersen¹,

Xiao³

2007

Cell Res

184

187

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npg In addition to well-defined DNA repair pathways, all living organisms have evolved mechanisms to avoid cell death caused by replication fork collapse at a site where replication is blocked due to disruptive covalent modifications of DNA. The term DNA damage tolerance (DDT) has been employed loosely to include a collection of mechanisms by which cells survive replication-blocking lesions with or without associated genomic instability. Recent genetic analyses indicate that DDT in eukaryotes, from yeast to human, consists of two parallel pathways with one being error-free and another highly mutagenic. Interestingly, in budding yeast, these two pathways are mediated by sequential modifications of the proliferating cell nuclear antigen (PCNA) by two ubiquitination complexes Rad6-Rad18 and Mms2-Ubc13-Rad5. Damage-induced monoubiquitination of PCNA by Rad6-Rad18 promotes translesion synthesis (TLS) with increased mutagenesis, while subsequent polyubiquitination of PCNA at the same K164 residue by Mms2-Ubc13-Rad5 promotes error-free lesion bypass. Data obtained from recent studies suggest that the above mechanisms are conserved in higher eukaryotes. In particular, mammals contain multiple specialized TLS polymerases. Defects in one of the TLS polymerases have been linked to genomic instability and cancer. DNA damage toleranceIn the presence of spontaneous or carcinogen-induced DNA damage, living cells have to maintain and complete DNA synthesis or risk replication fork collapse. Since the process of DNA licensing is to ensure the genome is duplicated once and only once during each cell cycle, stalled or collapsed replication forks may not be able to restart, which often results in double-strand breaks (DSBs) and causes compromised genome integrity or cell death. In addition to highly conserved DNA repair pathways, all living organisms have evolved schemes to ensure continuation of DNA synthesis in the presence of damage. These schemes were originally termed DNA postreplication repair (PRR) due to observations of transient shortened nascent DNA structures following S phase in response to DNA damage. In bacteria and unicellular yeast, these shortened DNA segments can be measured by an alkaline sedimentation assay [1] or directly observed in electron micrographs [2]. In wild-type cells, these truncated DNA segments were restored to full length following a short recovery time. One typical experiment [1] involved the restoration of the nascent strand following UV exposure in nucleotide excision repair (NER)-deficient cells and was originally assumed to represent a mechanism of DNA repair. However, further investigation revealed that, although the nascent fragments were re-annealed, the original UV-induced pyrimidine dimers, which were responsible for the generation of single-strand gaps, often persisted in the genome [3,4]. It was argued that the replication-blocking lesion was not necessarily corrected, but rather transiently bypassed and carried over to the next generation. Perhaps it is more beneficial for the organi...

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Section: Ddt In Prokaryotesmentioning

confidence: 99%

Section: Error-free Ddtmentioning

confidence: 99%

Eukaryotic DNA damage tolerance and translesion synthesis through covalent modifications of PCNA

Andersen¹,

Xiao³

2007

Cell Res

184

187

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“…Regression of a replication fork stalled at a single-strand lesion is well established in E. coli and is an ATP-requiring process. It may in principle apply to all types of lesions that stall the replication fork, including abasic sites (Robu et al, 2001). Recombination using information from the sister chromatid at stalled replication forks (Gruss and Michel, 2001), as well as translesion synthesis across abasic sites are well established processes in bacteria.…”

Section: Evolution Of Uracil-dna Glycosylasesmentioning

confidence: 99%

Uracil in DNA – occurrence, consequences and repair

2002

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“…As demonstrated by Michel and co-workers (22), inactivation of the replicative helicase DnaB leads to the formation of cleavable Holliday junction intermediates (the products of regression) in a process that is RecA-de-pendent. Additionally, RecA protein promotes an extensive regression of a DNA structure mimicking a stalled fork, with a gap on the leading strand, in an in vitro system (12). The RecA reaction documented in vivo (22) is distinct in terms of strand polarity to that studied in vitro (12).…”

mentioning

confidence: 99%

Situational Repair of Replication Forks

Robu

Inman

Cox

2004

Journal of Biological Chemistry

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Replication forks often stall or collapse when they encounter a DNA lesion. Fork regression is part of several major paths to the repair of stalled forks, allowing nonmutagenic bypass of the lesion. We have shown previously that Escherichia coli RecA protein can promote extensive regression of a forked DNA substrate that mimics a possible structure of a replication fork stalled at a leading strand lesion. Using electron microscopy and gel electrophoresis, we demonstrate that another protein, E. coli RecG helicase, promotes extensive fork regression in the same system. The RecG-catalyzed fork regression is very efficient and faster than the

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RecA protein promotes the regression of stalled replication forks in vitro

Cited by 149 publications

References 48 publications

Eukaryotic DNA damage tolerance and translesion synthesis through covalent modifications of PCNA

Eukaryotic DNA damage tolerance and translesion synthesis through covalent modifications of PCNA

Uracil in DNA – occurrence, consequences and repair

Situational Repair of Replication Forks

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