Sit down, relax and unwind: structural insights into RecQ helicase mechanisms

Killoran, Michael P.; Keck, James L.

doi:10.1093/nar/gkl538

Cited by 58 publications

(54 citation statements)

References 77 publications

(106 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…7 and 1a and 1b). The conserved sequence of some of the domains is slightly different and both of these proteins contain ATP binding and helicase C-terminal regions ( 42 In some RecQ proteins multiple HRDC domains are also present. 42 HRDC domain is an 80-amino acid domain usually found at the C-terminus of RecQ helicases and RNase D homologs from various organisms, including human, yeast and bacteria.…”

mentioning

confidence: 99%

“…The conserved sequence of some of the domains is slightly different and both of these proteins contain ATP binding and helicase C-terminal regions ( 42 In some RecQ proteins multiple HRDC domains are also present. 42 HRDC domain is an 80-amino acid domain usually found at the C-terminus of RecQ helicases and RNase D homologs from various organisms, including human, yeast and bacteria. 43 This domain is involved in the binding of protein to specific DNA structures (e.g., long-forked duplexes and Holliday junctions) that are formed during replication, recombination or transcription.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Genome wide identification of Plasmodium falciparum helicases: A comparison with human host

Tuteja

2010

Cell Cycle

View full text Add to dashboard Cite

mentioning

confidence: 99%

mentioning

confidence: 99%

Genome wide identification of Plasmodium falciparum helicases: A comparison with human host

Tuteja

2010

Cell Cycle

View full text Add to dashboard Cite

“…WRN has a modular composition (Fig. 6a) and structural studies on the protein's domains and those of homologues are helping to define WRN mediated functions (Killoran and Keck, 2006). The N-terminus of WRN contains the exonuclease domain, the central core contains the helicase region and in the C-terminus two regions have been identified that bind protein partners and/or DNA (Sharma et al, 2006).…”

Section: Double-strand Breaks Base Excision Repair and Wrnmentioning

confidence: 99%

“…This is similar to the Q motif in RNA DEAD-box helicases, indicating a possible evolutionary link between the two families. Mutations in the helicase motifs disrupt the function of RecQ helicases (Killoran and Keck, 2006). In WRN, a mutation in Motif I in mice induces a Werner phenotype in mice tail-derived fibroblasts (Wang et al, 2000).…”

Section: Double-strand Breaks Base Excision Repair and Wrnmentioning

confidence: 99%

Developing master keys to brain pathology, cancer and aging from the structural biology of proteins controlling reactive oxygen species and DNA repair

2007

View full text Add to dashboard Cite

This review is focused on proteins with key roles in pathways controlling either reactive oxygen species or DNA damage responses, both of which are essential for preserving the nervous system. An imbalance of reactive oxygen species or inappropriate DNA damage response likely causes mutational or cytotoxic outcomes, which may lead to cancer and/or aging phenotypes. Moreover, individuals with hereditary disorders in proteins of these cellular pathways have significant neurological abnormalities. Mutations in a superoxide dismutase, which removes oxygen free radicals, may cause the neurodegenerative disease amyotrophic lateral sclerosis. Additionally, DNA repair disorders that affect the brain to varying extents include ataxia-telangiectasia-like disorder, Cockayne syndrome or Werner syndrome. Here, we highlight recent advances gained through structural biochemistry studies on enzymes linked to these disorders and other related enzymes acting within the same cellular pathways. We describe the current understanding of how these vital proteins coordinate chemical steps and integrate cellular signaling and response events. Significantly, these structural studies may provide a set of master keys to developing a unified understanding of the survival mechanisms utilized after insults by reactive oxygen species and genotoxic agents, and also provide a basis for developing an informed intervention in brain tumor and neurodegenerative disease progression.

show abstract

“…RecQ family members have been found in diverse organisms, including bacteria, yeasts, fungi, flies, frogs, and humans. Prokaryotes and unicellular eukaryotes usually possess a single RecQ homologue, while multicellular organisms express multiple ones (4)(5)(6). In E. coli, RecQ[Ec] is the solitary RecQ helicase.…”

mentioning

confidence: 99%

Characterization of Biochemical Properties of Bacillus subtilis RecQ Helicase

et al. 2014

View full text Add to dashboard Cite

DNA helicases use the chemical energy derived from the binding and hydrolysis of ATP to catalyze the unwinding of double-stranded DNA (dsDNA). They are found in all living organisms and perform essential functions during DNA metabolism, including replication, transcription, repair, and recombination. The RecQ family helicases, which were named after the Escherichia coli RecQ (RecQ[Ec]) helicase (1, 2), belong to the superfamily (SF) 2 of DNA helicases (3). RecQ family members have been found in diverse organisms, including bacteria, yeasts, fungi, flies, frogs, and humans. Prokaryotes and unicellular eukaryotes usually possess a single RecQ homologue, while multicellular organisms express multiple ones (4-6). In E. coli, RecQ[Ec] is the solitary RecQ helicase. In humans, five family members, RECQ1, BLM, WRN, RECQ4, and RECQ5, have been identified. Mutations in BLM, WRN, and RECQ4 are linked to the human hereditary disorders Bloom, Werner, and Rothmund-Thomson syndromes, respectively. The affected individuals are characterized by a rapid onset of cancer, accelerated aging, growth abnormalities, and other defects (7). At the cellular level, the RecQ enzymes maintain genomic integrity through various mechanisms, such as dsDNA break repair (8).In E. coli, RecBCD is a major component of the dsDNA break (DSB) repair machinery. The RecQ[Ec] enzyme is active on both partially and fully duplex DNA substrates (2). In the absence of RecBCD in recBC sbcB sbcC mutant cells, RecQ [Ec] initiates homologous recombination for DSB repair via the RecF pathway, which is the major homologous recombination pathway for single-stranded DNA (ssDNA) gap repair (9, 10). In this pathway, RecQ[Ec] unwinds a DNA duplex or a duplex with a 3=-overhang to generate a 3=-terminated ssDNA, which is used for homologous pairing by the RecA protein (11, 12). The RecQ[Ec] enzyme also participates in the hybrid pathways, in which the parts of E. coli RecBCD and RecF recombination machines interexchange (13).In these pathways, RecQ[Ec] can initiate homologous recombination on the substrates that are not suitable for RecBCD (14, 15) because of its substrate specificity, which is wider than that of RecBCD (11). Furthermore, RecQ [Ec] can not only promote recombination but also disrupt joint molecule intermediates in vitro (10, 11). Thus, RecQ [Ec] contributes to recombination fidelity (16) and to recombinational repair without crossing over. Finally, RecQ[Ec] interacts functionally with topoisomerase III and therefore promotes the catenation and decatenation of dsDNA (17,18).The E. coli paradigm may not be valid for all other bacteria. At least for the DSB repair, different pathways are operative in Bacillus subtilis (19). B. subtilis is an aerobic, endospore-forming, rodshaped, Gram-positive bacterium commonly found in soil and water sources and in association with plants. Unlike E. coli, firmicutes may possess two RecQ-like homologues, RecQ [Bs] and RecS. These two homologous proteins might have some overlapping activities, and both are needed for t...

show abstract

Sit down, relax and unwind: structural insights into RecQ helicase mechanisms

Cited by 58 publications

References 77 publications

Genome wide identification of Plasmodium falciparum helicases: A comparison with human host

Genome wide identification of Plasmodium falciparum helicases: A comparison with human host

Developing master keys to brain pathology, cancer and aging from the structural biology of proteins controlling reactive oxygen species and DNA repair

Characterization of Biochemical Properties of Bacillus subtilis RecQ Helicase

Contact Info

Product

Resources

About