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Renu Tuteja - One of the best experts on this subject based on the ideXlab platform.
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Plasmodium falciparum Werner homologue is a nuclear protein and its biochemical activities reside in the N-terminal region
Protoplasma, 2016Co-Authors: Farhana Rahman, Mohammed Tarique, Moaz Ahmad, Renu TutejaAbstract:RecQ Helicases, also addressed as a gatekeeper of genome, are an inevitable family of genome scrutiny proteins conserved from prokaryotes to eukaryotes and play a vital role in DNA metabolism. The deficiencies of three RecQ proteins out of five are involved in genetic abnormalities like Bloom syndrome (BS), Werner syndrome (WS), and Rothmund–Thomson syndrome (RTS). It is noteworthy that Plasmodium falciparum contains only two members of the RecQ family as opposed to five members present in the host Homo sapiens . In the present study, we report the biochemical characterization of the homologue of Werner (Wrn) Helicase from P. falciparum 3D7 strain. Although there are significant sequence conservations between Wrn Helicases of both H. sapiens and P. falciparum as well as among all the other Plasmodium species, they contain some peculiar differences also. In silico studies reveal that PfWrn is evolutionarily close to the bacterial RecQ protein. The N-terminal fragment (PfWrnN) contains all the Helicase motifs along with all the functional domains and the predicted structure resembles with the human RecQ1 protein, whereas the C-terminal fragment (PfWrnC) contains no significant domain. Biochemical characterization further revealed that purified recombinant PfWrnN shows ATPase and DNA Helicase activity in 3′ to 5′ direction, but PfWrnC lacks the ATPase and Helicase activities. Immunofluorescence study shows that PfWrn is expressed in all the stages of intraerythrocytic development of the P. falciparum 3D7 strain and localizes distinctly in the nucleus. This study can be used for further characterization of RecQ Helicases that will aid in understanding the physiological significance of these Helicases in the malaria parasite.
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Genome-wide comprehensive analysis of human Helicases.
Communicative & Integrative Biology, 2014Co-Authors: Pavan Umate, Narendra Tuteja, Renu TutejaAbstract:Helicases are motor proteins that catalyze the unwinding of duplex nucleic acids in an ATP-dependent manner. They are involved in almost all the nucleic acid transactions. In the present study, we report a comprehensive analysis of Helicase gene family in human and its comparison with homologs in model organisms. The human genome encodes for 95 non-redundant Helicase proteins, of which 64 are RNA Helicases and 31 are DNA Helicases. 57 RNA Helicases are validated based on annotations and occurrence of conserved Helicase signature motifs. These include 14 DExH and 37 DExD subfamily members, six other members such as U5.snRNP, ATR-X, Suv3, FANCJ, and two of superkiller viralicidic activity 2-like Helicases. 31 DNA Helicases are also identified, which include RecQ, MCM and RuvB-like Helicases. Finding a set of Helicases in human and almost similar sequences in model organisms suggests that the "core" members of Helicase gene family are highly conserved throughout evolution. The present study gives an overview of members of RNA and DNA Helicases encoded by the human genome along with their conserved motifs, phylogeny and homologs in model organisms. The study on comparing these homologs will spread light on the organization and complexity of Helicase gene family in model organisms. The comprehensive analysis of human Helicases presented in this study will further provide an invaluable resource for elaborate biological research on these Helicases.
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Genome-wide analysis of Helicase gene family from rice and Arabidopsis: a comparison with yeast and human
Plant Molecular Biology, 2010Co-Authors: Pavan Umate, Renu Tuteja, Narendra TutejaAbstract:Helicases are motor proteins which can catalyze the unwinding of stable RNA or DNA duplex utilizing mainly ATP as source of energy. In this study we have identified complete sets of Helicases from rice and Arabidopsis . The Helicase gene family in rice and Arabidopsis contains 115 and 113 genes respectively. These Helicases were validated based on their annotations and supported with organization of conserved Helicase signature motifs. We have also identified homologs of 64 rice RNA and DNA Helicases in Arabidopsis , yeast and human. We explored Arabidopsis oligonucleotide array data to gain functional insights into the transcriptome of Helicase family members under ten different stress conditions. Our results revealed that expression of Helicase genes is profoundly regulated under various stress conditions. The Helicases identified in this study lay a foundation for the in depth characterization of each Helicase type.
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Structural and mechanistic aspect of DEAD-box Helicases
National Academy Science Letters-india, 2005Co-Authors: Narendra Tuteja, Ajay A. Vashisht, Renu TutejaAbstract:DFAD-box Helicases are ubiquitous enzymes that catalyze the unwinding of energetically stable duplex DNA (DNA Helicases) or duplex RNA secondary structures (RNA Helicases). DNA Helicases are involved in replication, repair, recombination, and transcription, while the DEAD-box RNA Helicases are involved in modulation of RNA structure and thereby influence RNA synthesis, splicing, replication, translation initiation, editing, rRNA processing, ribosome assembly, nuclear mRNA export, mRNA stabilization and degradation. They are associated with intrinsic ssDNA-dependent or RNA-dependent ATPase activities, which provide the energy for the Helicase action. Mechanistically, there are two classes of Helicases, those that can translocate 3'- to 5'-, or 5' to 3' directions with respect to the strand on which they initially bind. A hallmark of most of the Helicases (but not for all) is the existence of a set of nine highly conserved amino acid sequences called 'Helicase motifs', which are clustered together for Helicase function. One of the important Helicase motifs is DEAD (Asp-Glu-Ala-Asp) that is why the family of these proteins is called DEAD-box Helicases. PcrA Helicase from Bacillius stearothermophilus was the first Helicase whose crystal structure was solved in 1996 by an Indian scientist H. S. Subramanya in Dale B. Wigley's group at University of Oxford, UK. After this several DEAD-box Helicases have been crystallized and suggested a common structural fold for their function. Furthermore, the information on the function of conserved Helicase motifs and mechanism of DNA or RNA unwinding is also emerging. In this article we have covered possibly all the Helicases whose structure have been solved and the possible mechanisms of unwinding.
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Prokaryotic and eukaryotic DNA Helicases
FEBS Journal, 2004Co-Authors: Narendra Tuteja, Renu TutejaAbstract:DNA Helicases are ubiquitous molecular motor proteins which harness the chemical free energy of ATP hydrolysis to catalyze the unwinding of energetically stable duplex DNA, and thus play important roles in nearly all aspects of nucleic acid metabolism, including replication, repair, recombination, and transcription. They break the hydrogen bonds between the duplex helix and move unidirectionally along the bound strand. All Helicases are also translocases and DNA-dependent ATPases. Most contain conserved Helicase motifs that act as an engine to power DNA unwinding. All DNA Helicases share some common properties, including nucleic acid binding, NTP binding and hydrolysis, and unwinding of duplex DNA in the 3' to 5' or 5' to 3' direction. The minichromosome maintenance (Mcm) protein complex (Mcm4/6/7) provides a DNA-unwinding function at the origin of replication in all eukaryotes and may act as a licensing factor for DNA replication. The RecQ family of Helicases is highly conserved from bacteria to humans and is required for the maintenance of genome integrity. They have also been implicated in a variety of human genetic disorders. Since the discovery of the first DNA Helicase in Escherichia coli in 1976, and the first eukaryotic one in the lily in 1978, a large number of these enzymes have been isolated from both prokaryotic and eukaryotic systems, and the number is still growing. In this review we cover the historical background of DNA Helicases, Helicase assays, biochemical properties, prokaryotic and eukaryotic DNA Helicases including Mcm proteins and the RecQ family of Helicases. The properties of most of the known DNA Helicases from prokaryotic and eukaryotic systems, including viruses and bacteriophages, are summarized in tables.
Narendra Tuteja - One of the best experts on this subject based on the ideXlab platform.
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Genome-wide comprehensive analysis of human Helicases.
Communicative & Integrative Biology, 2014Co-Authors: Pavan Umate, Narendra Tuteja, Renu TutejaAbstract:Helicases are motor proteins that catalyze the unwinding of duplex nucleic acids in an ATP-dependent manner. They are involved in almost all the nucleic acid transactions. In the present study, we report a comprehensive analysis of Helicase gene family in human and its comparison with homologs in model organisms. The human genome encodes for 95 non-redundant Helicase proteins, of which 64 are RNA Helicases and 31 are DNA Helicases. 57 RNA Helicases are validated based on annotations and occurrence of conserved Helicase signature motifs. These include 14 DExH and 37 DExD subfamily members, six other members such as U5.snRNP, ATR-X, Suv3, FANCJ, and two of superkiller viralicidic activity 2-like Helicases. 31 DNA Helicases are also identified, which include RecQ, MCM and RuvB-like Helicases. Finding a set of Helicases in human and almost similar sequences in model organisms suggests that the "core" members of Helicase gene family are highly conserved throughout evolution. The present study gives an overview of members of RNA and DNA Helicases encoded by the human genome along with their conserved motifs, phylogeny and homologs in model organisms. The study on comparing these homologs will spread light on the organization and complexity of Helicase gene family in model organisms. The comprehensive analysis of human Helicases presented in this study will further provide an invaluable resource for elaborate biological research on these Helicases.
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Genome-wide analysis of Helicase gene family from rice and Arabidopsis: a comparison with yeast and human
Plant Molecular Biology, 2010Co-Authors: Pavan Umate, Renu Tuteja, Narendra TutejaAbstract:Helicases are motor proteins which can catalyze the unwinding of stable RNA or DNA duplex utilizing mainly ATP as source of energy. In this study we have identified complete sets of Helicases from rice and Arabidopsis . The Helicase gene family in rice and Arabidopsis contains 115 and 113 genes respectively. These Helicases were validated based on their annotations and supported with organization of conserved Helicase signature motifs. We have also identified homologs of 64 rice RNA and DNA Helicases in Arabidopsis , yeast and human. We explored Arabidopsis oligonucleotide array data to gain functional insights into the transcriptome of Helicase family members under ten different stress conditions. Our results revealed that expression of Helicase genes is profoundly regulated under various stress conditions. The Helicases identified in this study lay a foundation for the in depth characterization of each Helicase type.
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Structural and mechanistic aspect of DEAD-box Helicases
National Academy Science Letters-india, 2005Co-Authors: Narendra Tuteja, Ajay A. Vashisht, Renu TutejaAbstract:DFAD-box Helicases are ubiquitous enzymes that catalyze the unwinding of energetically stable duplex DNA (DNA Helicases) or duplex RNA secondary structures (RNA Helicases). DNA Helicases are involved in replication, repair, recombination, and transcription, while the DEAD-box RNA Helicases are involved in modulation of RNA structure and thereby influence RNA synthesis, splicing, replication, translation initiation, editing, rRNA processing, ribosome assembly, nuclear mRNA export, mRNA stabilization and degradation. They are associated with intrinsic ssDNA-dependent or RNA-dependent ATPase activities, which provide the energy for the Helicase action. Mechanistically, there are two classes of Helicases, those that can translocate 3'- to 5'-, or 5' to 3' directions with respect to the strand on which they initially bind. A hallmark of most of the Helicases (but not for all) is the existence of a set of nine highly conserved amino acid sequences called 'Helicase motifs', which are clustered together for Helicase function. One of the important Helicase motifs is DEAD (Asp-Glu-Ala-Asp) that is why the family of these proteins is called DEAD-box Helicases. PcrA Helicase from Bacillius stearothermophilus was the first Helicase whose crystal structure was solved in 1996 by an Indian scientist H. S. Subramanya in Dale B. Wigley's group at University of Oxford, UK. After this several DEAD-box Helicases have been crystallized and suggested a common structural fold for their function. Furthermore, the information on the function of conserved Helicase motifs and mechanism of DNA or RNA unwinding is also emerging. In this article we have covered possibly all the Helicases whose structure have been solved and the possible mechanisms of unwinding.
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Prokaryotic and eukaryotic DNA Helicases
FEBS Journal, 2004Co-Authors: Narendra Tuteja, Renu TutejaAbstract:DNA Helicases are ubiquitous molecular motor proteins which harness the chemical free energy of ATP hydrolysis to catalyze the unwinding of energetically stable duplex DNA, and thus play important roles in nearly all aspects of nucleic acid metabolism, including replication, repair, recombination, and transcription. They break the hydrogen bonds between the duplex helix and move unidirectionally along the bound strand. All Helicases are also translocases and DNA-dependent ATPases. Most contain conserved Helicase motifs that act as an engine to power DNA unwinding. All DNA Helicases share some common properties, including nucleic acid binding, NTP binding and hydrolysis, and unwinding of duplex DNA in the 3' to 5' or 5' to 3' direction. The minichromosome maintenance (Mcm) protein complex (Mcm4/6/7) provides a DNA-unwinding function at the origin of replication in all eukaryotes and may act as a licensing factor for DNA replication. The RecQ family of Helicases is highly conserved from bacteria to humans and is required for the maintenance of genome integrity. They have also been implicated in a variety of human genetic disorders. Since the discovery of the first DNA Helicase in Escherichia coli in 1976, and the first eukaryotic one in the lily in 1978, a large number of these enzymes have been isolated from both prokaryotic and eukaryotic systems, and the number is still growing. In this review we cover the historical background of DNA Helicases, Helicase assays, biochemical properties, prokaryotic and eukaryotic DNA Helicases including Mcm proteins and the RecQ family of Helicases. The properties of most of the known DNA Helicases from prokaryotic and eukaryotic systems, including viruses and bacteriophages, are summarized in tables.
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RNA Helicase-related genes of Plasmodium falciparum and Plasmodium cynomolgi.
Biochemical and Biophysical Research Communications, 1999Co-Authors: Ping Song, Narendra Tuteja, Pawan Malhotra, V. S. ChauhanAbstract:RNA Helicases play many essential roles including cell development and growth. Using degenerate oligonucleotide primers designed to amplify DNA fragments flanked by the highly conserved Helicase motifs VLDEAD and YIHRIG and genomic DNAs from the malarial parasites as a template, we have cloned two putative RNA Helicase genes (546 and 540 bp) fromP. falciparumand one gene (546 bp) fromP. cynomologi.Southern blot analysis revealed that these could be multiple and single-copy genes inP. falciparumandP. cynomolgi,respectively. Several members of the RNA Helicase gene family share sequence identity with malarial parasite's Helicases ranging from 30 to 76%, suggesting that they are functionally related. The discovery of such a multitude of putative RNA Helicase genes in malarial parasites suggested that RNA Helicase activities may be involved in many essential biological processes. Further characterization of these Helicases may also help in designing parasite-specific inhibitors/drugs which specifically inhibit the parasite's growth without affecting the host.
Raymond J Monnat - One of the best experts on this subject based on the ideXlab platform.
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altered recq Helicase expression in sporadic primary colorectal cancers
Translational Oncology, 2013Co-Authors: Piri Welcsh, Kelly T Carter, Jane L Meza, Nora Sarvetnick, Slavomir Dzieciatkowski, William M Grady, Suzanne M. Dintzis, Raymond J Monnat, Lawrence A LoebAbstract:Deregulation of DNA repair enzymes occurs in cancers and may create a susceptibility to chemotherapy. Expression levels of DNA repair enzymes have been shown to predict the responsiveness of cancers to certain chemotherapeutic agents. The RECQ Helicases repair damaged DNA including damage caused by topoisomerase I inhibitors, such as irinotecan. Altered expression levels of these enzymes in colorectal cancer (CRC) may influence the response of the cancers to irinotecan. Thus, we assessed RECQ Helicase (WRN, BLM, RECQL, RECQL4, and RECQL5) expression in primary CRCs, matched normal colon, and CRC cell lines. We found that BLM and RECQL4 mRNA levels are significantly increased in CRC (P = .0011 and P < .0001, respectively), whereas RECQL and RECQL5 are significantly decreased (P = .0103 and P = .0029, respectively). RECQ Helicase expression patterns varied between specific molecular subtypes of CRCs. The mRNA and protein expression of the majority of the RECQ Helicases was closely correlated, suggesting that altered mRNA expression is the predominant mechanism for deregulated RECQ Helicase expression. Immunohistochemistry localized the RECQ Helicases to the nucleus. RECQ Helicase expression is altered in CRC, suggesting that RECQ Helicase expression has potential to identify CRCs that are susceptible to specific chemotherapeutic agents.
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eLS - DNA Helicase‐deficiency Disorders
Encyclopedia of Life Sciences, 2010Co-Authors: Julia M. Sidorova, Raymond J MonnatAbstract:Deoxyribonucleic acid (DNA) Helicases use energy derived from the hydrolysis of adenosine triphosphate (ATP) to separate the complementary strands of DNA. This article focuses on one family of DNA Helicases, the human RECQ (recombination) Helicases and the syndromes that arise due to their deficiency. The five human RECQ Helicases share a common, conserved Helicase domain and all five proteins appear to play important roles in cellular DNA metabolism. Loss-of-function mutations in three family members cause the human cancer predisposition syndromes Bloom syndrome (BS), Werner syndrome (WS) and Rothmund–Thomson syndrome (RTS). This article outlines clinical features of the RECQ Helicase-deficiency syndromes and the underlying genetics, biochemistry and function of the associated human RECQ Helicase genes and proteins. We discuss how the loss of RECQ function may promote genetic instability and disease pathogenesis, and how RECQ Helicases may serve as predictors of cancer risk and the response to therapy. Key Concepts: RECQ Helicases are found in all Kingdoms of life. RECQ Helicases use the energy of ATP hydrolysis to unwind the strands of duplex DNA molecules. RECQ Helicases play important roles in many aspects of DNA metabolism including DNA replication and repair, recombination and telomere maintenance. Loss of RECQ Helicase function is associated with defects in DNA metabolism, genetic instability, reduced cell proliferation and cellular senescence or apoptosis. Heritable human RECQ Helicase deficiencies are rare. Three distinct autosomal recessive RECQ Helicase deficiency syndromes have been identified thus far. RECQ Helicase-deficient individuals have an elevated risk of cancer together with additional developmental or acquired findings. Acquired RECQ Helicase deficiencies may be common in adult cancer, where loss-of-function may modify the response to therapy. Keywords: RECQ Helicases; Bloom syndrome; Werner syndrome; Rothmund–Thomson syndrome; DNA replication; DNA repair; telomeres; homologous recombination; genetic instability; cancer predisposition syndrome
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human recq Helicases roles in dna metabolism mutagenesis and cancer biology
Seminars in Cancer Biology, 2010Co-Authors: Raymond J MonnatAbstract:Helicases use the energy of ATP hydrolysis to separate double-stranded nucleic acids to facilitate essential processes such as replication, recombination, transcription and repair. This article focuses on the human RECQ Helicase gene and protein family. Loss of function of three different members has been shown to cause Bloom syndrome (BS), Werner syndrome (WS) and Rothmund–Thomson syndrome (RTS). This article outlines clinical and cellular features of these cancer predisposition syndromes, and discusses their pathogenesis in light of our understanding of RECQ Helicase biochemical activities and in vivo functions. I also discuss the emerging role for RECQ Helicases as predictors of disease risk and the response to therapy.
Kevin D. Raney - One of the best experts on this subject based on the ideXlab platform.
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Structure and function of Pif1 Helicase.
Biochemical Society Transactions, 2017Co-Authors: Alicia K. Byrd, Kevin D. RaneyAbstract:Pif1 family Helicases have multiple roles in the maintenance of nuclear and mitochondrial DNA in eukaryotes. Saccharomyces cerevisiae Pif1 is involved in replication through barriers to replication, such as G-quadruplexes and protein blocks, and reduces genetic instability at these sites. Another Pif1 family Helicase in S. cerevisiae, Rrm3, assists in fork progression through replication fork barriers at the rDNA locus and tRNA genes. ScPif1 (Saccharomyces cerevisiae Pif1) also negatively regulates telomerase, facilitates Okazaki fragment processing, and acts with polymerase δ in break-induced repair. Recent crystal structures of bacterial Pif1 Helicases and the Helicase domain of human PIF1 combined with several biochemical and biological studies on the activities of Pif1 Helicases have increased our understanding of the function of these proteins. This review article focuses on these structures and the mechanism(s) proposed for Pif1's various activities on DNA.
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fine tuning of a dna fork by the recq Helicase
Proceedings of the National Academy of Sciences of the United States of America, 2015Co-Authors: Alicia K. Byrd, Kevin D. RaneyAbstract:Helicases are enzymes that couple the hydrolysis of ATP to the unwinding of duplex nucleic acids (NAs), thus providing the single-stranded NA (ssNA) intermediates necessary for nucleic acid processing and maintenance such as replication, recombination, repair, and transcription (1⇓–3). All Helicases possess a core Helicase domain containing RecA-like motifs that are responsible for NA binding and ATP hydrolysis. Variation among individual Helicases and Helicase families within both the Helicase core and in accessory domains allows this single class of enzymes to perform a myriad of different functions within the cell in different manners on various substrate types, resulting in Helicases specific for every process involving NA in the cell. In PNAS, Rad et al. (4) provide a close-up view of a member of the RecQ family of enzymes that can modulate its activity to “fine tune” unwinding at a DNA fork. When DNA needs to be unwound, a Helicase is typically involved. Unwinding produces a DNA fork structure, but the number of base pairs melted and the rate of melting are modulated to fit the needed task. For example, DNA replication requires a highly processive Helicase activity, whereas some forms of DNA repair might require only a few base pairs to be melted. DNA recombination can involve unwinding of a few base pairs, … [↵][1]1To whom correspondence may be addressed. Email: akbyrd{at}uams.edu or raneykevind{at}uams.edu. [1]: #xref-corresp-1-1
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Protein displacement by Helicases.
Methods of Molecular Biology, 2009Co-Authors: Laxmi Yeruva, Kevin D. RaneyAbstract:Helicases are ubiquitous enzymes that are vital to all living organisms. They are motor proteins that move in a specific direction along the nucleic acid and unwind the nucleic acid (DNA and RNA). ATP hydrolysis provides energy for Helicase translocation and unwinding. The unwinding process provides ssDNA intermediates necessary for replication, recombination, and repair. Mutations in specific DNA Helicases can lead to disruption in DNA metabolism. For example, mutations in Helicases genes resulted in diseases such as xeroderma pigmentosum, cockayne's syndrome, Bloom's syndrome, and Werner's syndrome. During unwinding, Helicases are most likely to encounter proteins while moving along the nucleic acid. Several different research groups have demonstrated that Helicases shift or displace proteins from one nucleic acid-bound location to another. These protein-protein collisions could result in displacement of proteins from nucleic acid or dissociation of Helicase from nucleic acid. This report describes several different methods developed to study protein displacement by DNA and RNA Helicases.
Stephen C Kowalczykowski - One of the best experts on this subject based on the ideXlab platform.
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recq Helicase and topoisomerase iii comprise a novel dna strand passage function a conserved mechanism for control of dna recombination
Molecular Cell, 1999Co-Authors: Frank G Harmon, Russell J Digate, Stephen C KowalczykowskiAbstract:E. coli RecQ protein is a multifunctional Helicase with homologs that include the S. cerevisiae Sgs1 Helicase and the H. sapiens Wrn and Blm Helicases. Here we show that RecQ Helicase unwinds a covalently closed double-stranded DNA (dsDNA) substrate and that this activity specifically stimulates E. coli topoisomerase III (Topo III) to fully catenate dsDNA molecules. We propose that these proteins functionally interact and that their shared activity is responsible for control of DNA recombination. RecQ Helicase has a comparable effect on the Topo III homolog of S. cerevisiae, consistent with other RecQ and Topo III homologs acting together in a similar capacity. These findings highlight a novel, conserved activity that offers insight into the function of the other RecQ-like Helicases.
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recq Helicase in concert with reca and ssb proteins initiates and disrupts dna recombination
Genes & Development, 1998Co-Authors: Frank G Harmon, Stephen C KowalczykowskiAbstract:RecQ Helicase is important to homologous recombination and DNA repair in Escherichia coli. We demonstrate that RecQ Helicase, in conjunction with RecA and SSB proteins, can initiate recombination events in vitro. In addition, RecQ protein is capable of unwinding a wide variety of DNA substrates, including joint molecules formed by RecA protein. These data are consistent with RecQ Helicase assuming two roles in the cell; it can be (1) an initiator of homologous recombination, or (2) a disrupter of joint molecules formed by aberrant recombination. These findings also shed light on the function of the eukaryotic homologs of RecQ Helicase, the Sgs1, Blm, and Wrn Helicases.
