Chromosome Breakage Is Regulated by the Interaction of the BLM Helicase and Topoisomerase IIα

Russell, Beatriz; Bhattacharyya, Saumitri; Keirsey, Jeremy; Sandy, April; Grierson, Patrick; Perchiniak, Erin; Kavecansky, Juraj; Acharya, Samir; Groden, Joanna

doi:10.1158/0008-5472.can-10-1727

Cited by 21 publications

(43 citation statements)

References 42 publications

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“…Previously, human topoisomerase II␣ and topoisomerase I were reported to inhibit the BLM and WRN helicases, respectively, through inhibition of their ATPase activity (43,44); in contrast, human TopoIII␣ had no effect on BLM ATPase activity (9). We found that the Hel112 DNA-independent ATPase activity was not affected by 2-fold molar excess of SsTop3 (Fig.…”

Section: Resultsmentioning

confidence: 52%

Synergic and Opposing Activities of Thermophilic RecQ-like Helicase and Topoisomerase 3 Proteins in Holliday Junction Processing and Replication Fork Stabilization

Valenti

Felice

Perugino

et al. 2012

Journal of Biological Chemistry

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Background: RecQ helicases and topoisomerase 3 enzymes play essential functions in all DNA activities, and their malfunctioning is associated with genomic instability. Results: A RecQ-like helicase and topoisomerase 3 from thermophilic archaea interact physically and functionally. Conclusion:The thermophilic enzymes show synergic and antagonistic activities on different DNA substrates. Significance: The results suggest a novel mechanism of modulation of RecQ-like helicases by topoisomerase 3 enzymes.

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Section: Resultsmentioning

confidence: 52%

Synergic and Opposing Activities of Thermophilic RecQ-like Helicase and Topoisomerase 3 Proteins in Holliday Junction Processing and Replication Fork Stabilization

Valenti

Felice

Perugino

et al. 2012

Journal of Biological Chemistry

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“…Recently, it was shown that BLM helicase and Topoisomerase IIα interact to maintain genomic integrity (24). Although this interaction served to stimulate BLM helicase activity, BLM helicase was not reported to stimulate DNA decatenation (24).…”

Section: Resultsmentioning

confidence: 99%

RECQL5 cooperates with Topoisomerase II alpha in DNA decatenation and cell cycle progression

Ramamoorthy

Tadokoro

Rybanská

et al. 2011

Nucleic Acids Research

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DNA decatenation mediated by Topoisomerase II is required to separate the interlinked sister chromatids post-replication. SGS1, a yeast homolog of the human RecQ family of helicases interacts with Topoisomerase II and plays a role in chromosome segregation, but this functional interaction has yet to be identified in higher organisms. Here, we report a physical and functional interaction of Topoisomerase IIα with RECQL5, one of five mammalian RecQ helicases, during DNA replication. Direct interaction of RECQL5 with Topoisomerase IIα stimulates the decatenation activity of Topoisomerase IIα. Consistent with these observations, RECQL5 co-localizes with Topoisomerase IIα during S-phase of the cell cycle. Moreover, cells with stable depletions of RECQL5 display a slow proliferation rate, a G2/M cell cycle arrest and late S-phase cycling defects. Metaphase spreads generated from RECQL5-depleted cells exhibit undercondensed and entangled chromosomes. Further, RECQL5-depleted cells activate a G2/M checkpoint and undergo apoptosis. These phenotypes are similar to those observed when Topoisomerase II catalytic activity is inhibited. These results reveal an important role for RECQL5 in the maintenance of genomic stability and a new insight into the decatenation process.

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“…Stable depletion of RECQL5 inhibits cell proliferation and induces a G 2 /M checkpoint. BLM also interacts with Topo IIα, which is important in preventing chromosomal breakage (228). These observations indicate that RecQ helicases play significant roles in the resolution of late replication intermediates and DNA decatenation.…”

Section: Recq Helicases In Dna Replicationmentioning

confidence: 99%

Human RecQ Helicases in DNA Repair, Recombination, and Replication

Croteau

Popuri

Opresko

et al. 2014

Annu. Rev. Biochem.

481

521

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RecQ helicases are an important family of genome surveillance proteins conserved from bacteria to humans. Each of the five human RecQ helicases plays critical roles in genome maintenance and stability, and the RecQ protein family members are often referred to as guardians of the genome. The importance of these proteins in cellular homeostasis is underscored by the fact that defects in BLM, WRN, and RECQL4 are linked to distinct heritable human disease syndromes. Each human RecQ helicase has a unique set of protein-interacting partners, and these interactions dictate its specialized functions in genome maintenance, including DNA repair, recombination, replication, and transcription. Human RecQ helicases also interact with each other, and these interactions have significant impact on enzyme function. Future research goals in this field include a better understanding of the division of labor among the human RecQ helicases and learning how human RecQ helicases collaborate and cooperate to enhance genome stability.

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Chromosome Breakage Is Regulated by the Interaction of the BLM Helicase and Topoisomerase IIα

Cited by 21 publications

References 42 publications

Synergic and Opposing Activities of Thermophilic RecQ-like Helicase and Topoisomerase 3 Proteins in Holliday Junction Processing and Replication Fork Stabilization

Synergic and Opposing Activities of Thermophilic RecQ-like Helicase and Topoisomerase 3 Proteins in Holliday Junction Processing and Replication Fork Stabilization

RECQL5 cooperates with Topoisomerase II alpha in DNA decatenation and cell cycle progression

Human RecQ Helicases in DNA Repair, Recombination, and Replication

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