Human RECQL5β stimulates flap endonuclease 1

Speina, Elżbieta; Dawut, Lale; Hedayati, Mohammad; Wang, Zhengming; May, Alfred; Schwendener, Sybille; Janscak, Pavel; Croteau, Deborah L.; Bohr, Vilhelm A.

doi:10.1093/nar/gkp1217

Cited by 25 publications

(35 citation statements)

References 57 publications

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“…Several of the RecQ helicases, including BLM [32], WRN [33], RECQL4 [34] and RECQ5β [35], have been found to stimulate the 5′-flap incision of FEN1. Hence, based on the physical interaction observed between hSuv3 and FEN1, we tested whether the interaction could modulate the catalytic activity of one or both of the proteins.…”

Section: Resultsmentioning

confidence: 99%

“…Helicase-independent stimulation of FEN1 activity has also been shown for WRN, BLM, RecQ4 and RecQ5 [32–35]. The interaction between WRN and FEN1 has previously been proposed to be involved in initiation of recombination pathways at stalled replication forks by employing FEN1’s GEN activity [27].…”

Section: Discussionmentioning

confidence: 99%

“…FEN1 plays a critical role in DNA repair, homologous recombination, telomere maintenance, RNA primer removal and resolution of stalled replication forks [27–30]. Although at present a potential relationship between FEN1 and RECQ1 has not been characterized [31], stimulation of FEN1 in the presence of BLM [32], WRN [33], RECQL4 [34] and RECQ5β [35] has been reported.…”

Section: Introductionmentioning

confidence: 99%

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The human Suv3 helicase interacts with replication protein A and flap endonuclease 1 in the nucleus

Venø

Kulikowicz

Pestana

et al. 2011

Biochemical Journal

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The hSuv3 (human Suv3) helicase has been shown to be a major player in mitochondrial RNA surveillance and decay, but its physiological role might go beyond this functional niche. hSuv3 has been found to interact with BLM (Bloom’s syndrome protein) and WRN (Werner’s syndrome protein), members of the RecQ helicase family involved in multiple DNA metabolic processes, and in protection and stabilization of the genome. In the present study, we have addressed the possible role of hSuv3 in genome maintenance by examining its potential association with key interaction partners of the RecQ helicases. By analysis of hSuv3 co-IP (co-immunoprecipitation) complexes, we identify two new interaction partners of hSuv3: the RPA (replication protein A) and FEN1 (flap endonuclease 1). Utilizing an in vitro biochemical assay we find that low amounts of RPA inhibit helicase activity of hSuv3 on a forked substrate. Another single-strand-binding protein, mtSSB (mitochondrial single-strand-binding protein), fails to affect hSuv3 activity, indicating that the functional interaction is specific for hSuv3 and RPA. Further in vitro studies demonstrate that the flap endonuclease activity of FEN1 is stimulated by hSuv3 independently of flap length. hSuv3 is generally thought to be a mitochondrial helicase, but the physical and functional interactions between hSuv3 and known RecQ helicase-associated proteins strengthen the hypothesis that hSuv3 may play a significant role in nuclear DNA metabolism as well.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The human Suv3 helicase interacts with replication protein A and flap endonuclease 1 in the nucleus

Venø

Kulikowicz

Pestana

et al. 2011

Biochemical Journal

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“…For instance, RECQL5 physically interacts with human Flap Endonuclease 1 (FEN1), which plays a critical role in the processing of Okazaki fragments during DNA replication and dramatically stimulates the rate of FEN1 cleavage on both 5′ flap and nicked DNA substrates (Speina et al , 2010). This raises the intriguing possibility that RECQL5, via stimulation of FEN1, could also coordinate the cleavage event needed to reset an uncoupled replication fork (Speina et al , 2010). Furthermore, RECQL5 can promote strand exchange on synthetic DNA structures that resemble a stalled replication fork.…”

Section: Role Of Recql5 In Dna Replication and Chromosomal Segregationmentioning

confidence: 99%

Human RECQL5: Guarding the crossroads of DNA replication and transcription and providing backup capability

Popuri

Tadokoro

Croteau

et al. 2013

Critical Reviews in Biochemistry and Molecular Biology

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DNA helicases are ubiquitous enzymes that catalyze unwinding of duplex DNA and function in all metabolic processes in which access to single-stranded DNA is required, including DNA replication, repair, recombination and RNA transcription. RecQ helicases are a conserved family of DNA helicases that display highly specialized and vital roles in the maintenance of genome stability. Mutations in three of the five human RecQ helicases, BLM, WRN and RECQL4 are associated with the genetic disorders Bloom syndrome, Werner syndrome and Rothmund-Thomson syndrome that are characterized by chromosomal instability, premature aging and predisposition to cancer. The biological role of human RECQL5 is only partially understood and RECQL5 has not yet been associated with any human disease. Illegitimate recombination and replication stress are hallmarks of human cancers and common instigators for genomic instability and cell death. Recql5 knockout mice are cancer prone and show increased chromosomal instability. Recql5-deficient mouse embryonic fibroblasts are sensitive to camptothecin and display elevated levels of sister chromatid exchanges. Unlike other human RecQ helicases, RECQL5 is recruited to single-stranded DNA breaks and is also proposed to play an essential role in RNA transcription. Here, we review the established roles of RECQL5 at the cross roads of DNA replication, recombination and transcription, and propose that human RECQL5 provides important backup functions in the absence of other DNA helicases.

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“…In humans, WRN, BLM, and RecQ5, the human homologues of yeast RecQ are an example of Fen1 stimulator (Brosh et al, 2001;Wang et al, 2005;Speina et al, 2010). Recently, it was shown that Dna2 and Pif1 can contribute to rapid nick formation by stimulating FEN1 (Henry et al, 2008).…”

Section: Speculations On the Presence Of Numerous Stimulators Of Dna2mentioning

confidence: 99%

Lagging Strand Synthesis and Genomic Stability

Nguyen¹,

Lee²,

Seo³

2011

DNA Repair - On the Pathways to Fixing DNA Damage and Errors

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Human RECQL5β stimulates flap endonuclease 1

Cited by 25 publications

References 57 publications

The human Suv3 helicase interacts with replication protein A and flap endonuclease 1 in the nucleus

The human Suv3 helicase interacts with replication protein A and flap endonuclease 1 in the nucleus

Human RECQL5: Guarding the crossroads of DNA replication and transcription and providing backup capability

Lagging Strand Synthesis and Genomic Stability

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