Identification within the simian virus 40 genome of a chromosomal loop attachment site that contains topoisomerase II cleavage sites

Pommier, ﻿Yves; Cockerill, Peter N.; Kohn, Kurt W.; Garrard, William T.

doi:10.1128/jvi.64.1.419-423.1990

Cited by 47 publications

(17 citation statements)

References 53 publications

(50 reference statements)

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“…We have recently shown that in the presence of purified topoisomerase H, the most active anthracyclines induce prominent cleavage in a small region of the entire SV40 DNA, between nucleotides 4200 and 4300 (6). This SV40 region also corresponds to a cluster of major enzyme sites in the absence of drug and to a nuclear matrix attachment region (MAR) (7). In the present study, the DNA sequence of topoisomerase H cleavage sites induced in the presence and absence of doxorubicin was analyzed in several segment of the SV40 genome including the MAR in order to investigate the molecular basis for the sequence-selectivity of doxorubicin action upon topoisomerase H. The analysis of doxorubicin-induced sites was limited to the effects of low doxorubicin concentrations (never exceeding 0.5 uM) since doxorubicin induces maximum cleavage at relatively low drug concentrations (between 0.5 and 2 uM) and suppresses DNA cleavage at higher concentrations (6).…”

Section: Introductionmentioning

confidence: 99%

Local sequence requirements for DNA cleavage by mammalian topoisomerase II in the presence of doxorubicin

1990

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Doxorubicin, a DNA-intercalator, is one of several anti-cancer drugs that have been found to stabilizes topoisomerase II cleavage complexes at drug-specific DNA sites. The distribution and DNA sequence environments of doxorubicin-stabilized sites were determined in the SV40 genome. The sites were found to be most concentrated in the major nuclear matrix-associated region and nearly absent in the vicinity of the replication origin including the enhancer sequences in the 21-bp and 72-bp tandem repeats. Among 97 doxorubicin-stabilized sites that were localized at the DNA sequence level, none coincided with any of the 90 topoisomerase II cleavage sites detected in the same regions in the absence of drug. Cleavage at the 90 enzyme-only sites was inhibited by doxorubicin and never stimulated even at low drug concentrations. All of the doxorubicin-stabilized sites had an A at the 3' terminus of at least one member of each pair of strand breaks that would constitute a topoisomerase II double-strand scission. Conversely, none of the enzyme-only sites had an A simultaneously at the corresponding positions on opposite strands. The 3'-A requirement for doxorubicin-stabilized cleavage is therefore incompatible with enzyme-only cleavage and explains the mutual exclusivity of the two classes of sites.

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Section: Introductionmentioning

confidence: 99%

Local sequence requirements for DNA cleavage by mammalian topoisomerase II in the presence of doxorubicin

1990

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“…The NM is the binding site for MARs. These are a class of cis ‐regulatory elements, typically representing 200–300 bp, AT‐rich DNA sequences and occurring at an average of 1 for every 30 kb of eukaryotic DNA 5, 6, 7, 8, 9. MARs possess high affinity to the isolated NM 10, 11, 12, 13, 14, 15.…”

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confidence: 99%

Direct interaction with and activation of p53 by SMAR1 retards cell‐cycle progression at G₂/M phase and delays tumor growth in mice

Kaul

Mukherjee

Ahmed

et al. 2002

Intl Journal of Cancer

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The tumor-suppressor p53 is a multifunctional protein mainly responsible for maintaining genomic integrity. p53 induces its tumor-suppressor activity by either causing cellcycle arrest (G 1 /S or G 2 /M) or inducing cells to undergo apoptosis. This function of wild-type p53 as "guardian of the genome" is presumably achieved by forming molecular complexes with different DNA targets as well as by interacting with a number of cellular proteins, e.g., Mdm2, Gadd45, p21, 14-3-3, Bax and Apaf-1. Upon activation, p53 activates p21, which in turn controls the cell cycle by regulating G 1 or G 2 checkpoints. Here, we report SMAR1 as one such p53-interacting protein that is involved in delaying tumor progression in vivo as well as in regulating the cell cycle. SMAR1S activates p53-mediated reporter gene expression in mouse melanoma cells, breast cancer cells (MCF-7) and p53 null cells (K562), followed by activation of its downstream effector, p21. We further demonstrate that SMAR1 physically interacts and colocalizes with p53. These data together suggest that SMAR1 is the only known MARBP that delays tumor progression via direct activation and interaction with tumor-suppressor p53.

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“…This is reminiscent of observations made for three other DNA viruses, simian virus 40 (SV40), adenoviruses, and Epstein-Barr virus. In the SV40 genome a MAR sequence has been mapped to a 300-bp segment central to the large T-antigen gene (47), which may help the SV40 genome to be preferentially associated with nuclear structures (14). The adenovirus genome has been found attached to the nuclear matrix in the form of episomal DNA, and this may occur with the help of the adenovirus-encoded protein covalently bound to the termini of the viral genome (52).…”

Section: The Genomes Of Genital Hpvs Have a Highly Conserved Pattern mentioning

confidence: 99%

“…Cellular DNA has been found to be tightly associated with the nuclear matrix through specific DNA elements which have been termed matrix attachment regions (MARs). Similar elements occur in DNA viruses (14,30,47,52). MARs may be up to a few hundred nucleotides in length but do not demonstrate strictly conserved sequence motifs, although many contain A-T-rich stretches and clusters of topoisomerase II cleavage sites (23).…”

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confidence: 99%

Nuclear Matrix Attachment Regions of Human Papillomavirus Type 16 Point toward Conservation of These Genomic Elements in All Genital Papillomaviruses

Tan

Bartsch

Schwarz

et al. 1998

J Virol

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The gene functions, transcriptional regulation, and genome replication of human papillomaviruses (HPVs) have been extensively studied. Thus far, however, there has been little research on the organization of HPV genomes in the nuclei of infected cells. As a first step to understand how chromatin and suprachromatin structures may modulate the life cycles of these viruses, we have identified and mapped interactions of HPV DNAs with the nuclear matrix. The endogenous genomes of HPV type 16 (HPV-16) which are present in SiHa, HPKI, and HPKII cells, adhere in vivo to the nuclear matrixes of these cell lines. A tight association with the nuclear matrix in vivo may be common to all genital HPV types, as the genomes of HPV-11, HPV-16, HPV-18, and HPV-33 showed high affinity in vitro to preparations of the nuclear matrix of C33A cells, as did the well-known nuclear matrix attachment region (MAR) of the cellular beta interferon gene. Affinity to the nuclear matrix is not evenly spread over the HPV-16 genome. Five genomic segments have strong MAR properties, while the other parts of the genome have low or no affinity. Some of the five MARs correlate with known cis-responsive elements: a strong MAR lies in the 5′ segment of the long control region (LCR), and another one lies in the E6 gene, flanking the HPV enhancer, the replication origin, and the E6 promoter. The strongest MAR coincides with the E5 gene and the early-late intergenic region. Weak MAR activity is present in the E1 and E2 genes and in the 3′ part of L2. The in vitro map of MAR activity appears to reflect MAR properties in vivo, as we found for two selected fragments with and without MAR activity. As is typical for many MARs, the two segments with highest affinity, namely, the 5′ LCR and the early-late intergenic region, have an extraordinarily high A-T content (up to 85%). It is likely that these MARs have specific functions in the viral life cycle, as MARs predicted by nucleotide sequence analysis, patterns of A-T content, transcription factor YY1 binding sites, and likely topoisomerase II cleavage sites are conserved in similar positions throughout all genital HPVs.

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Identification within the simian virus 40 genome of a chromosomal loop attachment site that contains topoisomerase II cleavage sites

Cited by 47 publications

References 53 publications

Local sequence requirements for DNA cleavage by mammalian topoisomerase II in the presence of doxorubicin

Local sequence requirements for DNA cleavage by mammalian topoisomerase II in the presence of doxorubicin

Direct interaction with and activation of p53 by SMAR1 retards cell‐cycle progression at G₂/M phase and delays tumor growth in mice

Nuclear Matrix Attachment Regions of Human Papillomavirus Type 16 Point toward Conservation of These Genomic Elements in All Genital Papillomaviruses

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Identification within the simian virus 40 genome of a chromosomal loop attachment site that contains topoisomerase II cleavage sites

Cited by 47 publications

References 53 publications

Local sequence requirements for DNA cleavage by mammalian topoisomerase II in the presence of doxorubicin

Local sequence requirements for DNA cleavage by mammalian topoisomerase II in the presence of doxorubicin

Direct interaction with and activation of p53 by SMAR1 retards cell‐cycle progression at G2/M phase and delays tumor growth in mice

Nuclear Matrix Attachment Regions of Human Papillomavirus Type 16 Point toward Conservation of These Genomic Elements in All Genital Papillomaviruses

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Direct interaction with and activation of p53 by SMAR1 retards cell‐cycle progression at G₂/M phase and delays tumor growth in mice