Rep Provides a Second Motor at the Replisome to Promote Duplication of Protein-Bound DNA

Guy, Colin P.; Atkinson, John D.; Gupta, Milind Kumar; Mahdi, Akeel A.; Gwynn, Emma J.; Rudolph, Christian J.; Moon, Peter B.; Knippenberg, I.C. van; Cadman, Chris J.; Dillingham, Mark S.; Lloyd, Robert G.; McGlynn, Peter

doi:10.1016/j.molcel.2009.11.009

Cited by 156 publications

(407 citation statements)

References 52 publications

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“…Superfamily 1 helicases that translocate 3′-5′ along ssDNA (E. coli Rep and UvrD and Bacillus stearothermophilus PcrA) promote movement of E. coli replisomes through nucleoprotein complexes, whereas D. radiodurans RecD2 and bacteriophage T4 Dda, 5′-3′ superfamily 1 helicases do not (10). Indeed, addition of RecD2 results in an apparent increase in the degree of replication blockage at protein-DNA complexes in vitro (10).…”

Section: Recd2 Inhibits Resumption Of Replication By Paused Replisomesmentioning

confidence: 99%

“…Indeed, addition of RecD2 results in an apparent increase in the degree of replication blockage at protein-DNA complexes in vitro (10). We investigated the basis for this apparent increase in fork blockage by RecD2.…”

Section: Recd2 Inhibits Resumption Of Replication By Paused Replisomesmentioning

confidence: 99%

“…If forks pause at such barriers and lose function, then replisome reloading, often via blocked fork processing by recombination enzymes, is required to resume genome duplication (4), an error-prone process associated with gross chromosomal rearrangements (5)(6)(7). However, pausing of replisomes does not necessarily lead to fork breakdown, because paused replisomes can continue duplication upon removal or bypass of the block (8)(9)(10)(11). The balance between resumption of replication versus breakdown of paused forks is therefore a critical factor in the maintenance of genome stability.…”

mentioning

confidence: 99%

“…Forks halted by nucleoprotein complexes can resume replication upon spontaneous dissociation of the nucleoprotein complex or active removal of the block by the replisome itself or accessory motors acting at the fork (9,10,(12)(13)(14). Similarly, a replisome encountering a lesion that inhibits synthesis by one of the polymerases may continue replication downstream of the lesion by repriming DNA synthesis.…”

mentioning

confidence: 99%

“…Wild-type Escherichia coli can survive expression of RecD2 but chromosomal DNA content is perturbed significantly, indicating that replisomes do pause frequently in vivo. Cells lacking a helicase, Rep, that clears protein-DNA barriers ahead of forks (10,22) are hypersensitive to RecD2 expression. In contrast, defects in base or nucleotide excision repair do not render RecD2 toxic.…”

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confidence: 99%

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Protein–DNA complexes are the primary sources of replication fork pausing in Escherichia coli

Gupta

Guy

Yeeles

et al. 2013

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

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105

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Replication fork pausing drives genome instability, because any loss of paused replisome activity creates a requirement for reloading of the replication machinery, a potentially mutagenic process. Despite this importance, the relative contributions to fork pausing of different replicative barriers remain unknown. We show here that Deinococcus radiodurans RecD2 helicase inactivates Escherichia coli replisomes that are paused but still functional in vitro, preventing continued fork movement upon barrier removal or bypass, but does not inactivate elongating forks. Using RecD2 to probe replisome pausing in vivo, we demonstrate that most pausing events do not lead to replisome inactivation, that transcription complexes are the primary sources of this pausing, and that an accessory replicative helicase is critical for minimizing the frequency and/or duration of replisome pauses. These findings reveal the hidden potential for replisome inactivation, and hence genome instability, inside cells. They also demonstrate that efficient chromosome duplication requires mechanisms that aid resumption of replication by paused replisomes, especially those halted by protein-DNA barriers such as transcription complexes.DNA repair | genome stability | Rep | RNA polymerase | recombination

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Section: Recd2 Inhibits Resumption Of Replication By Paused Replisomesmentioning

confidence: 99%

Section: Recd2 Inhibits Resumption Of Replication By Paused Replisomesmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Protein–DNA complexes are the primary sources of replication fork pausing in Escherichia coli

Gupta

Guy

Yeeles

et al. 2013

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

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105

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Replication fork pausing at protein barriers on chromosomes

Hizume

Araki

2019

FEBS Letters

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When a cell divides prior to completion of DNA replication, serious DNA damage may occur. Thus, in addition to accuracy, the processivity of the replication forks is important. DNA synthesis at replication forks should be completed in time, and forks overcome aberrant structures on the template DNA, including damaged sites, using trans‐lesion synthesis, occasionally introducing mutations. By contrast, the protein barrier built on the DNA is known to block the progression of replication forks at specific chromosomal loci. Such protein barriers avert any collision of replication and transcription machineries, or control the recombination of specific loci. The components and the mechanisms of action of protein barriers have been revealed mainly using genetic and biochemical techniques. In addition to proteins involved in replication fork pausing, the interaction of the replicative helicase and DNA polymerase is also essential for replication fork pausing. Here, we provide an overview of replication fork pausing at protein barriers.

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Clues to transcription/replication collision‐induced DNA damage: it was RNAP, in the chromosome, with the fork

Cooke,

Herman,

Sivaramakrishnan

2024

FEBS Letters

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DNA replication and RNA transcription processes compete for the same DNA template and, thus, frequently collide. These transcription–replication collisions are thought to lead to genomic instability, which places a selective pressure on organisms to avoid them. Here, we review the predisposing causes, molecular mechanisms, and downstream consequences of transcription–replication collisions (TRCs) with a strong emphasis on prokaryotic model systems, before contrasting prokaryotic findings with cases in eukaryotic systems. Current research points to genomic structure as the primary determinant of steady‐state TRC levels and RNA polymerase regulation as the primary inducer of excess TRCs. We review the proposed mechanisms of TRC‐induced DNA damage, attempting to clarify their mechanistic requirements. Finally, we discuss what drives genomes to select against TRCs.

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Rep Provides a Second Motor at the Replisome to Promote Duplication of Protein-Bound DNA

Cited by 156 publications

References 52 publications

Protein–DNA complexes are the primary sources of replication fork pausing in Escherichia coli

Protein–DNA complexes are the primary sources of replication fork pausing in Escherichia coli

Replication fork pausing at protein barriers on chromosomes

Clues to transcription/replication collision‐induced DNA damage: it was RNAP, in the chromosome, with the fork

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