Biochemical Characterization of Warsaw Breakage Syndrome Helicase

Wu, Yuliang; Sommers, Joshua A.; Khan, Irfan; Winter, Johan P. de; Brosh, Robert M.

doi:10.1074/jbc.m111.276022

Cited by 91 publications

(144 citation statements)

References 44 publications

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“…We have recently reported that Chl1 exhibits both genetic and physical interactions with Fen1 (Rudra and Skibbens, 2012). On the basis of these studies, Chl1 probably acts behind DNA polymerase during maturation of sister chromatids in order to facilitate cohesin loading by resolving aberrant DNA structures that might arise during Okazaki fragment maturation (Rudra and Skibbens, 2012;Wu et al, 2012). If correct, then establishment (and possibly deposition) occurs during histone deposition onto the newly replicated DNA -raising the possibility that cohesion, condensation and chromatinization are spatially and functionally coordinated (Fig.…”

Section: A Code For All Processesmentioning

confidence: 99%

Cohesin codes – interpreting chromatin architecture and the many facets of cohesin function

Rudra

Skibbens

2013

Journal of Cell Science

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SummarySister chromatid tethering is maintained by cohesin complexes that minimally contain Smc1, Smc3, Mcd1 and Scc3. During S-phase, chromatin-associated cohesins are modified by the Eco1/Ctf7 family of acetyltransferases. Eco1 proteins function during S phase in the context of replicated sister chromatids to convert chromatin-bound cohesins to a tethering-competent state, but also during G2 and M phases in response to double-stranded breaks to promote error-free DNA repair. Cohesins regulate transcription and are essential for ribosome biogenesis and complete chromosome condensation. Little is known, however, regarding the mechanisms through which cohesin functions are directed. Recent findings reveal that Eco1-mediated acetylation of different lysine residues in Smc3 during S phase promote either cohesion or condensation. Phosphorylation and SUMOylation additionally impact cohesin functions. Here, we posit the existence of a cohesin code, analogous to the histone code introduced over a decade ago, and speculate that there is a symphony of posttranslational modifications that direct cohesins to function across a myriad of cellular processes. We also discuss evidence that outdate the notion that cohesion defects are singularly responsible for cohesion-mutant-cell inviability. We conclude by proposing that cohesion establishment is linked to chromatin formation.

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Section: A Code For All Processesmentioning

confidence: 99%

Cohesin codes – interpreting chromatin architecture and the many facets of cohesin function

Rudra

Skibbens

2013

Journal of Cell Science

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“…G4 DNA can be bound and unwound by RECQ helicases (10), and by the XPD-related helicases such as human XPD (19) and its paralogs FANCJ (20,21), CHL1 (22), and likely RTEL1 (23). In the human genome, G4 motifs are greatly enriched near transcription start sites (TSS), at the 5′ end of first introns, and in exons and introns of many oncogenes (reviewed in refs.…”

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confidence: 99%

Regulation of gene expression by the BLM helicase correlates with the presence of G-quadruplex DNA motifs

Nguyen

Tang²,

Robles

et al. 2014

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

109

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Significance Bloom syndrome is a rare human genetic disease characterized by proportional dwarfism, immunodeficiency, and an elevated risk of many different cancer types. We used RNA expression profiling to identify networks of mRNAs and microRNAs that are differentially expressed in cells from Bloom syndrome patients and associated with cell proliferation, survival, and molecular pathways promoting cancer. Altered mRNA expression was in some cases strongly correlated with the presence of G4 motifs, which may form G-quadruplex targets that are bound by BLM. Further analysis of the genetic networks we identified may elucidate mechanisms responsible for Bloom syndrome disease pathogenesis and ways to ameliorate or prevent disease in affected individuals.

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“…ChlR1 interacts with Ctf18-RFC, PCNA, and FEN-1 and stimulates FEN-1 endonuclease activity on an equilibrating flap DNA structure, a model intermediate substrate that forms during lagging strand synthesis (35). ChlR1 unwinds G-quadruplex (G4) DNA with a strong preference for a twostranded antiparallel G4 (G2Ј) substrate and is only marginally active on a four-stranded parallel G4 structure (36). It was proposed that ChlR1 involvement in lagging strand processing during cellular DNA replication may be important for sister chromatid cohesion (37).…”

mentioning

confidence: 99%

A Distinct Triplex DNA Unwinding Activity of ChlR1 Helicase

Guo

Hundseth

Ding

et al. 2015

Journal of Biological Chemistry

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Background: DNA triplex helix structures are alternate DNA structures that can be a source of genomic instability. Results: ChlR1 helicase has a novel and distinct triplex DNA unwinding activity. Conclusion: ChlR1 defends genome integrity by resolving triplex DNA structures. Significance: The processing of triplex DNA substrates by proteins such as ChlR1 plays critical roles in genome maintenance.

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Biochemical Characterization of Warsaw Breakage Syndrome Helicase

Cited by 91 publications

References 44 publications

Cohesin codes – interpreting chromatin architecture and the many facets of cohesin function

Cohesin codes – interpreting chromatin architecture and the many facets of cohesin function

Regulation of gene expression by the BLM helicase correlates with the presence of G-quadruplex DNA motifs

A Distinct Triplex DNA Unwinding Activity of ChlR1 Helicase

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