hnRNP proteins and B23 are the major proteins of the internal nuclear matrix of HeLa S3 cells

Mattern, Karin; Humbel, Bruno M.; Muijsers, Anton O.; Jong, Luitzen de; Driel, Roel van

doi:10.1002/(sici)1097-4644(199608)62:2<275::aid-jcb15>3.0.co;2-k

Cited by 113 publications

(77 citation statements)

References 93 publications

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“…Such a key role of hnRNP-U in BER of oxidative DNA damage, probably in association with transcription, was quite unexpected. These results, together with the fact that hnRNP-U, also identified independently as scaffold attachment factor A, is a major component of the nuclear matrix (47), suggest a critical dynamic role of the nuclear architecture in the repair of oxidized bases during transcription (48).…”

Section: Discussionmentioning

confidence: 86%

Preferential Repair of Oxidized Base Damage in the Transcribed Genes of Mammalian Cells

Banerjee

Mandal

Das

et al. 2011

Journal of Biological Chemistry

128

150

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Preferential repair of bulky DNA adducts from the transcribed genes via nucleotide excision repair is well characterized in mammalian cells. However, definitive evidence is lacking for similar repair of oxidized bases, the major endogenous DNA lesions. Here we show that the oxidized base-specific human DNA glycosylase NEIL2 associates with RNA polymerase II and the transcriptional regulator heterogeneous nuclear ribonucleoprotein-U (hnRNP-U), both in vitro and in cells. NEIL2 immunocomplexes from cell extracts preferentially repaired the mutagenic cytosine oxidation product 5-hydroxyuracil in the transcribed strand. In a reconstituted system, we also observed NEIL2-initiated transcription-dependent base excision repair of 5-hydroxyuracil in the transcribed strand, with hnRNP-U playing a critical role. Chromatin immunoprecipitation/reimmunoprecipitation studies showed association of NEIL2, RNA polymerase II, and hnRNP-U on transcribed but not on transcriptionally silent genes. Furthermore, NEIL2-depleted cells accumulated more DNA damage in active than in silent genes. These results strongly support the preferential role of NEIL2 in repairing oxidized bases in the transcribed genes of mammalian cells.

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Section: Discussionmentioning

confidence: 86%

Preferential Repair of Oxidized Base Damage in the Transcribed Genes of Mammalian Cells

Banerjee

Mandal

Das

et al. 2011

Journal of Biological Chemistry

128

150

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“…Nucleophosmin copurifies with the nuclear matrix (25), and it seems reasonable to suggest that it is the interaction between this protein and CTCF that leads to the appearance of CTCF in the matrix fraction. Chromatin immunoprecipitation experiments have shown that nucleophosmin and CTCF colocalize at insulator sites in vivo, presumably explaining our observation that the HS4 insulator sequence is also concentrated in the matrix fraction.…”

Section: Discussionmentioning

confidence: 99%

“…Standard PCR of matrix DNA was carried out in 25-l reactions [2.5 l of 10X buffer͞0.5 l of 10 mM dNTP mix͞0.5 l each of 10 M forward and reverse primer͞0. 25 PCRs were carried out with 6C2 cell genomic DNA. Primer sequences are available on request.…”

Section: Methodsmentioning

confidence: 99%

The 5′-HS4 chicken β-globin insulator is a CTCF-dependent nuclear matrix-associated element

Yusufzai

Felsenfeld

2004

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

146

128

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The protein CTCF plays an essential role in the action of a widely distributed class of vertebrate enhancer-blocking insulators, of which the first example was found in a DNA sequence element, HS4, at the 5 end of the chicken ␤-globin locus. HS4 contains a binding site for CTCF that is necessary and sufficient for insulator action. Purification of CTCF has revealed that it interacts with proteins involved in subnuclear architecture, notably nucleophosmin, a 38-kDa nucleolar phosphoprotein that is concentrated in nuclear matrix preparations. In this report we show that both CTCF and the HS4 insulator element are incorporated in the matrix; HS4 incorporation depends on the presence of an intact CTCF-binding site. However the DNA sequence in the neighborhood of HS4 is not like that of canonical matrix attachment regions, and its incorporation into the matrix fraction is not sensitive to ribonuclease, suggesting that the insulator is a distinct matrix-associated element.I nsulators are DNA sequence elements that can act either to block the extension of a condensed chromatin domain into a transcriptionally active region (barrier activity), or to prevent the interaction of a distal enhancer with a promoter when placed between the two (1, 2). Elements with the latter property, called enhancer blocking insulators, have been found in Drosophila and in vertebrates. In flies the most studied insulator element is gypsy, which when placed between two enhancers in a series of enhancers found in the yellow locus, blocks the action of all enhancers distal to the insertion but has no effect on those more proximal to the promoter (3). It has been shown that the insulator action of gypsy is mediated by a DNA-binding protein, Suppressor of Hairy wing [Su(Hw)], and a cofactor, Mod(mdg4) (4). Gypsy elements appear to localize to the nuclear envelope, where they cluster and organize the neighboring chromatin into loop domains (5). It is thought that the loop domain structure gives rise to the insulating activity either by preventing regulatory elements on different loops from interacting or by interfering with a ''tracking'' signal that would ordinarily proceed from enhancer to promoter (6-8). Loop domains can be established by attachment to other fixed sites in the nucleus. For example, a barrier function that prevents heterochromatinization of an active gene can be generated by tethering DNA elements to nuclear pore proteins (9). Loop domains can also arise simply from interactions that cause the insulator-bound proteins to stick to each other.A different enhancer blocking insulator activity has been described in vertebrates. First found at the 5Ј end of the chicken ␤-globin locus, it is part of a compound element (HS4) at that site that has both barrier and enhancer-blocking action (10). These two activities are separable; the enhancer-blocking insulation arises from a single DNA site that binds the protein CTCF (11). Insulator elements that bind CTCF have also been found at many other loci including the human and mouse ␤-globin cl...

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“…In addition, a proteolytic product of the C proteins, unwinding protein 2 (UP2), influences the activity of DNA polymerase ␣, suggesting that hnRNPs C1 and C2 may also influence some aspects of DNA metabolism (29)(30)(31). Many of the hnRNP proteins, including hnRNPs C1 and C2, associate with the nuclear matrix (18,42,43). Interestingly, telomeres and the DNA replication machinery are also associated with this nuclear structure (14), and DNA polymerases ␣/primase are required for telomerase activity (15).…”

Section: Discussionmentioning

confidence: 99%

Heterogeneous Nuclear Ribonucleoproteins C1 and C2 Associate with the RNA Component of Human Telomerase

Ford

Suh

Wright

et al. 2000

Molecular and Cellular Biology

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Here we demonstrate that heterogeneous nuclear ribonucleoproteins (hnRNPs) C1 and C2 can associate directly with the integral RNA component of mammalian telomerase. The binding site for hnRNPs C1 and C2 maps to a 6-base uridylate tract located directly 5 to the template region in the human telomerase RNA (TR) and a 4-base uridylate tract directly 3 to the template in the mouse TR. Telomerase activity is precipitated with antibodies specific to hnRNPs C1 and C2 from cells expressing wild-type human TR but not a variant of the human TR lacking the hnRNPs C1 and C2 binding site, indicating that hnRNPs C1 and C2 require the 6-base uridylate tract within the human TR to associate with the telomerase holoenzyme. In addition, we demonstrate that binding of hnRNPs C1 and C2 to telomerase correlates with the ability of telomerase to access the telomere. Although correlative, these data do suggest that the binding of hnRNPs C1 and C2 to telomerase may be important for the ability of telomerase to function on telomeres. The C proteins of the hnRNP particle are also capable of colocalizing with telomere binding proteins, suggesting that the C proteins may associate with telomeres in vivo. Therefore, human telomerase is capable of associating with core members of the hnRNP family of RNA binding proteins through a direct and sequence-specific interaction with the human TR. This is also the first account describing the precise mapping of a sequence in the human TR that is required to associate with an auxiliary component of the human telomerase holoenzyme.Telomeres have many functions, including organizing chromosomes during meiosis, protecting chromosome ends from nucleolytic digestion and end-to-end fusion events, and facilitating complete replication of the chromosomes (3, 22, 64). During normal lagging strand replication of linear chromosomes, the ends are left with a gap between the final RNA priming event and the terminus (48,63). In the absence of any compensatory mechanism, telomere length decreases with each cell division cycle until the cell reaches a state of proliferative failure. Thus, telomeres also serve as a source of expendable DNA, avoiding the loss of coding DNA sequences.Telomerase is a cellular ribonucleoprotein reverse transcriptase that can maintain the length of telomeres by using its integral RNA component as a template for the addition of TTAGGG repeats onto the 3Ј end of linear chromosomes.

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hnRNP proteins and B23 are the major proteins of the internal nuclear matrix of HeLa S3 cells

Cited by 113 publications

References 93 publications

Preferential Repair of Oxidized Base Damage in the Transcribed Genes of Mammalian Cells

Preferential Repair of Oxidized Base Damage in the Transcribed Genes of Mammalian Cells

The 5′-HS4 chicken β-globin insulator is a CTCF-dependent nuclear matrix-associated element

Heterogeneous Nuclear Ribonucleoproteins C1 and C2 Associate with the RNA Component of Human Telomerase

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