A novel DNA-binding motif shares structural homology to DNA replication and repair nucleases and polymerases

Yuan, Yate-Ching; Whitson, Robert H.; Liu, Qin; Itakura, Keiichi; Chen, Yuan

doi:10.1038/2934

Cited by 54 publications

(56 citation statements)

References 33 publications

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“…It has previously been reported that the structure formed by O, O1, and O2 helices of pol I shares structural homology with a novel DNA binding motif (24) found in transcription factor Mrf-2 and in some DNA repair proteins such as E. coli endonuclease III (25) and T4 RNase H (24,26). This structural homology suggested the involvement of this motif in the recognition of double-stranded nucleic acid.…”

Section: Properties Of Sermentioning

confidence: 91%

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Participation of the Fingers Subdomain of Escherichia coli DNA Polymerase I in the Strand Displacement Synthesis of DNA

Singh

Srivastava

Patel³

et al. 2007

Journal of Biological Chemistry

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The replication of the genome requires the removal of RNA primers from the Okazaki fragments and their replacement by DNA. In prokaryotes, this process is completed by DNA polymerase I by means of strand displacement DNA synthesis and 5-nuclease activity. Here, we demonstrate that the strand displacement DNA synthesis is facilitated by the collective participation of Ser 769 , Phe 771 , and Arg 841 present in the fingers subdomain of DNA polymerase I. The steady and presteady state kinetic analysis of the properties of appropriate mutant enzymes suggest that: (a) Ser 769 and Phe 771 together are involved in the strand separation via the formation of a flap structure, and (b) Arg 841 interacts with the template strand to achieve the optimal strand separation and DNA synthesis. The amino acid residues Ser 769 and Phe 771 are constituents of the O1-helix, which together with O and O2 helices form a 3-helix bundle structure. We note that this 3-helix bundle motif also exists in prokaryotic RNA polymerase. Thus in both DNA and RNA polymerases, this motif may have been adopted to achieve the strand separation function.Strand displacement synthesis is an essential process in the removal and replacement of RNA primer moieties of Okazaki fragments. In prokaryotes, DNA polymerase I (pol I) 3 carries out this function by its 5Ј-nuclease and 5Ј-3Ј polymerase activities. Whereas early studies indicate a coordination of 5Ј-nuclease with the polymerase activity (1), the precise mechanism underlying this process is not clear. It appears that the participation of 5Ј-nuclease activity is not necessary for the strand displacement synthesis because the Klenow fragment of Escherichia coli DNA polymerase I has been known to catalyze strand displacement DNA synthesis (2). Thus, the strand separation activity resides in the polymerase domain of pol I.Despite the availability of numerous DNA-bound structures of polymerases (3-8), no significant information pertaining to strand displacement could be discerned because none of these crystal structures contained sufficiently long single-stranded template overhang or a downstream doublestranded DNA. One exception to this is the DNA-bound crystal structure of mammalian DNA polymerase ␤, where the enzyme-DNA complex contains gapped DNA (9). However, this enzyme has no strand displacement activity. In the DNA-bound crystal structures of pol I family DNA polymerases, the immediate unpaired template nucleotide assumes a flipped conformation (6) such that it cannot pair with the incoming dNTP substrate. The base moiety of the template (n ϩ 1) 4 nucleotide is positioned out of the DNA helical axis by more than 90°(4, 10, 11). In the enzyme-DNA-dNTP bound ternary complex, this nucleotide rearranges its conformation and pairs with the incoming dNTP substrate (6). In the crystal structures of polymerases, because of the short length of the single-stranded template overhang, only few interactions of downstream DNA with the enzyme protein could be discerned (3, 4, 6 -8, 11-13 4 The numbering scheme for...

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Section: Properties Of Sermentioning

confidence: 91%

“…This structural homology suggested the involvement of this motif in the recognition of double-stranded nucleic acid. However, for the DNA polymerase I family of enzymes, it was suggested that this region may be important in the binding of the ssDNA template overhang (24).…”

Section: Properties Of Sermentioning

confidence: 99%

Participation of the Fingers Subdomain of Escherichia coli DNA Polymerase I in the Strand Displacement Synthesis of DNA

Singh

Srivastava

Patel³

et al. 2007

Journal of Biological Chemistry

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“…Although these ARID domains are conserved from humans to yeast, their DNA-binding specificities may not be conserved. The solution structures of two different ARID domains have recently been reported (24,49).…”

Section: Discussionmentioning

confidence: 99%

A Specificity and Targeting Subunit of a Human SWI/SNF Family-Related Chromatin-Remodeling Complex

Nie

Xue

Yang

et al. 2000

Molecular and Cellular Biology

276

254

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The SWI/SNF family of chromatin-remodeling complexes facilitates gene activation by assisting transcription machinery to gain access to targets in chromatin. This family includes BAF (also called hSWI/SNF-A) and PBAF (hSWI/SNF-B) from humans and SWI/SNF and Rsc from Saccharomyces cerevisiae. However, the relationship between the human and yeast complexes is unclear because all human subunits published to date are similar to those of both yeast SWI/SNF and Rsc. Also, the two human complexes have many identical subunits, making it difficult to distinguish their structures or functions. Here we describe the cloning and characterization of BAF250, a subunit present in human BAF but not PBAF. BAF250 contains structural motifs conserved in yeast SWI1 but not in any Rsc components, suggesting that BAF is related to SWI/SNF. BAF250 is also a homolog of the Drosophila melanogaster Osa protein, which has been shown to interact with a SWI/SNFlike complex in flies. BAF250 possesses at least two conserved domains that could be important for its function. First, it has an AT-rich DNA interaction-type DNA-binding domain, which can specifically bind a DNA sequence known to be recognized by a SWI/SNF family-related complex at the ␤-globin locus. Second, BAF250 stimulates glucocorticoid receptor-dependent transcriptional activation, and the stimulation is sharply reduced when the C-terminal region of BAF250 is deleted. This region of BAF250 is capable of interacting directly with the glucocorticoid receptor in vitro. Our data suggest that BAF250 confers specificity to the human BAF complex and may recruit the complex to its targets through either protein-DNA or protein-protein interactions.

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“…It was identified in our laboratory in 1996 as a novel nuclear protein that binds to sequences upstream of the human cytomegalovirus major immediate-early enhancer/promoter and exerts repressor activity in undifferentiated human Tera-2 cells (1). Subsequent studies revealed the three-dimensional structure of the novel DNA-binding motif (ARID) of Mrf-2 and mechanisms of DNA recognition (2)(3)(4). The ARID family of DNA-binding proteins has grown since then to include fifteen proteins found in humans and most other vertebrate species, and six proteins found in Drosophila as well as proteins found in worms, fungi, plants and yeast (5)(6)(7)(8).…”

Section: Arid5b (At-rich Interaction Domain-containingmentioning

confidence: 99%

Knockdown of AT-rich interaction domain (ARID) 5B gene expression induced AMPKα2 activation in cardiac myocytes

Hirose-Yotsuya

Okamoto

Yamakawa

et al. 2015

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A novel DNA-binding motif shares structural homology to DNA replication and repair nucleases and polymerases

Cited by 54 publications

References 33 publications

Participation of the Fingers Subdomain of Escherichia coli DNA Polymerase I in the Strand Displacement Synthesis of DNA

Participation of the Fingers Subdomain of Escherichia coli DNA Polymerase I in the Strand Displacement Synthesis of DNA

A Specificity and Targeting Subunit of a Human SWI/SNF Family-Related Chromatin-Remodeling Complex

Knockdown of AT-rich interaction domain (ARID) 5B gene expression induced AMPKα2 activation in cardiac myocytes

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