Replication fork pausing at protein barriers on chromosomes

Hizume, Kohji; Araki, Hideki

doi:10.1002/1873-3468.13481

Cited by 20 publications

(23 citation statements)

References 108 publications

(126 reference statements)

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“…Failure to bypass these barriers may result in genome instability, which can lead to cellular abnormalities and genetic disease. Cells contain various accessory helicases that help the replisome bypass these difficult barriers (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). A subset of these helicases act on the opposite strand of the replicative helicase (1,2,14,19).…”

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confidence: 99%

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Replisome bypass of a protein-based R-loop block by Pif1

Schauer

Spenkelink

Lewis

et al. 2020

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

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Efficient and faithful replication of the genome is essential to maintain genome stability. Replication is carried out by a multiprotein complex called the replisome, which encounters numerous obstacles to its progression. Failure to bypass these obstacles results in genome instability and may facilitate errors leading to disease. Cells use accessory helicases that help the replisome bypass difficult barriers. All eukaryotes contain the accessory helicase Pif1, which tracks in a 5′–3′ direction on single-stranded DNA and plays a role in genome maintenance processes. Here, we reveal a previously unknown role for Pif1 in replication barrier bypass. We use an in vitro reconstitutedSaccharomyces cerevisiaereplisome to demonstrate that Pif1 enables the replisome to bypass an inactive (i.e., dead) Cas9 (dCas9) R-loop barrier. Interestingly, dCas9 R-loops targeted to either strand are bypassed with similar efficiency. Furthermore, we employed a single-molecule fluorescence visualization technique to show that Pif1 facilitates this bypass by enabling the simultaneous removal of the dCas9 protein and the R-loop. We propose that Pif1 is a general displacement helicase for replication bypass of both R-loops and protein blocks.

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confidence: 99%

“…All eukaryotes contain an accessory helicase, Pif1, which tracks in a 5′-3′ direction on single-stranded DNA (ssDNA) (11)(12)(13)(14)(15)(16). Pif1 is important in pathways such as Okazaki-fragment processing and break-induced repair that require the removal of DNA-binding proteins as well as potential displacement of Rloops (11-13, 21, 15-18, 22-25).…”

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confidence: 99%

Replisome bypass of a protein-based R-loop block by Pif1

Schauer

Spenkelink

Lewis

et al. 2020

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

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“…DNA is also frequently damaged in normal growth conditions due to exposure to endogenous and exogenous DNA damaging agents. The resulting DNA nicks and mismatches also present significant obstacles for normal replication (17)(18)(19).…”

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confidence: 99%

Tetrameric UvrD helicase is located at theE. colireplisome due to frequent replication blocks

Wollman

Syeda

Leech

et al. 2021

Preprint

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DNA replication in all organisms must overcome nucleoprotein blocks to complete genome duplication. Accessory replicative helicases in Escherichia coli, Rep and UvrD, help replication machinery overcome blocks by removing incoming nucleoprotein complexes or aiding the re-initiation of replication. Mechanistic details of Rep function have emerged from recent live cell studies, however, the activities of UvrD in vivo remain unclear. Here, by integrating biochemical analysis and super-resolved single-molecule fluorescence microscopy, we discovered that UvrD self-associates into a tetramer and, unlike Rep, is not recruited to a specific replisome protein despite being found at approximately 80% of replication forks. By deleting rep and DNA repair factors mutS and uvrA, perturbing transcription by mutating RNA polymerase, and antibiotic inhibition; we show that the presence of UvrD at the fork is dependent on its activity. This is likely mediated by the very high frequency of replication blocks due to DNA bound proteins, including RNA polymerase, and DNA damage. UvrD is recruited to sites of nucleoprotein blocks via distinctly different mechanisms to Rep and therefore plays a more important and complementary role than previously realised in ensuring successful DNA replication.

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“…We are, thus, delighted to present you with the successful outcome: 17 Review articles [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] and 2 Research articles [18,19] on topics as diverse as plant biology, evolutionary biology, chromatin, translation, the cytoskeleton, mitochondria and translational research.…”

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confidence: 99%

“…Chris Tyler‐Smith (The Welcome Sanger Institute, UK) and colleagues discuss the contribution of genomic analyses to our understanding of classic selective sweeps . Moreover, Hiroyuki Araki (National Institute of Genetics, Japan) and Kohji Hisume (Saitama Medical University, Japan) review replication fork pausing at chromosomal protein barriers .…”

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confidence: 99%

The 44th FEBS Congress in Krakow: celebrating the multidisciplinarity of biological research

Wieland¹

2019

FEBS Letters

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Replication fork pausing at protein barriers on chromosomes

Cited by 20 publications

References 108 publications

Replisome bypass of a protein-based R-loop block by Pif1

Replisome bypass of a protein-based R-loop block by Pif1

Tetrameric UvrD helicase is located at theE. colireplisome due to frequent replication blocks

The 44th FEBS Congress in Krakow: celebrating the multidisciplinarity of biological research

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