Site-Specific DNA Cleavage byChlorellaVirus Topoisomerase II†

Biochemistry ◽  
2002 ◽  
Vol 41 (39) ◽  
pp. 11761-11769 ◽  
Author(s):  
John M. Fortune ◽  
Jennifer S. Dickey ◽  
Oleg V. Lavrukhin ◽  
James L. Van Etten ◽  
R. Stephen Lloyd ◽  
...  
Keyword(s):  
Dna Cleavage ◽  
Topoisomerase Ii ◽  
Site Specific

scholarly journals Site-specific DNA cleavage within the MLL breakpoint cluster region induced by topoisomerase II inhibitors [see comments]

Blood ◽  
1996 ◽  
Vol 87 (7) ◽  
pp. 2649-2658 ◽  
Author(s):  
PD Aplan ◽  
DS Chervinsky ◽  
M Stanulla ◽  
WC Burhans
Keyword(s):  
Dna Cleavage ◽  
Topoisomerase Ii ◽  
Model Systems ◽  
Site Specific ◽  
Breakpoint Cluster Region ◽  
Cluster Region ◽  
Topoisomerase Ii Inhibitors ◽  
Mll Gene ◽  
Secondary Leukemias ◽  
Double Strand Dna

The MLL gene located at 11q23 is frequently disrupted by chromosomal translocation in a wide spectrum of newly diagnosed acute leukemias. Recently, it has become apparent that the MLL gene is very frequently disrupted by chromosomal translocations in patients with secondary leukemias associated with chemotherapeutic regimens incorporating topoisomerase II inhibitors. These secondary leukemias associated with topoisomerase II inhibitors (most commonly teniposide, etoposide, or doxorubicin) have distinct clinical and biologic features which have led to the speculation that they are induced by treatment with topoisomerase II inhibitors. We have identified a site within the MLL breakpoint cluster region (bcr) that is highly sensitive to double- strand DNA cleavage induced by topoisomerase II inhibitors. This finding is quite specific and highly reproducible. Although it was initially discovered in malignant lymphoblasts isolated from a patient receiving multiagent chemotherapy, this site-specific double-strand DNA cleavage can be induced in tissue culture using malignant cell lines as well as peripheral blood from normal individuals. Site-specific cleavage occurs in a significant fraction of cells using a variety of model systems, is both time and dose dependent, and can be induced with either doxorubicin or etoposide. This site-specific cleavage maps to the same region as a consensus topoisomerase II cleavage site within the MLL bcr. These results suggest that site specific cleavage within the MLL bcr induced by topoisomerase II inhibitors may be an early step leading to MLL translocations and secondary leukemia.

Stimulation of Site-Specific Topoisomerase II-Mediated DNA Cleavage by an N-Methylpyrrolecarboxamide-anilinoacridine Conjugate: Relation to DNA Binding

Biochemistry ◽  
1994 ◽  
Vol 33 (33) ◽  
pp. 9865-9874 ◽  
Author(s):  
Philippe Fosse ◽  
Brigitte Rene ◽  
Jean-Marie Saucier ◽  
Jean-Pierre Henichart ◽  
Michael J. Waring ◽  
...  
Keyword(s):  
Dna Binding ◽  
Dna Cleavage ◽  
Topoisomerase Ii ◽  
Site Specific ◽  
Stimulation Of

Stimulation by γ-carboline derivatives (simplified analogues of antitumor ellipticines) of site specific DNA cleavage by calf DNA topoisomerase II

1990 ◽  
Vol 39 (4) ◽  
pp. 669-676 ◽  
Author(s):  
Philippe Fossé ◽  
Brigitte René ◽  
Jean-Marie Saucier ◽  
Chi Hung Nguyen ◽  
Emile Bisagni ◽  
...  
Keyword(s):  
Dna Cleavage ◽  
Topoisomerase Ii ◽  
Dna Topoisomerase Ii ◽  
Dna Topoisomerase ◽  
Site Specific

scholarly journals DNA cleavage within the MLL breakpoint cluster region is a specific event which occurs as part of higher-order chromatin fragmentation during the initial stages of apoptosis.

1997 ◽  
Vol 17 (7) ◽  
pp. 4070-4079 ◽  
Author(s):  
M Stanulla ◽  
J Wang ◽  
D S Chervinsky ◽  
S Thandla ◽  
P D Aplan
Keyword(s):  
Dna Cleavage ◽  
Cellular Response ◽  
Topoisomerase Ii ◽  
Apoptotic Cell ◽  
Chemotherapeutic Agents ◽  
Higher Order ◽  
Site Specific ◽  
Breakpoint Cluster Region ◽  
Cluster Region ◽  
Topo Ii

A distinct population of therapy-related acute myeloid leukemia (t-AML) is strongly associated with prior administration of topoisomerase II (topo II) inhibitors. These t-AMLs display distinct cytogenetic alterations, most often disrupting the MLL gene on chromosome 11q23 within a breakpoint cluster region (bcr) of 8.3 kb. We recently identified a unique site within the MLL bcr that is highly susceptible to DNA double-strand cleavage by classic topo II inhibitors (e.g., etoposide and doxorubicin). Here, we report that site-specific cleavage within the MLL bcr can be induced by either catalytic topo II inhibitors, genotoxic chemotherapeutic agents which do not target topo II, or nongenotoxic stimuli of apoptotic cell death, suggesting that this site-specific cleavage is part of a generalized cellular response to an apoptotic stimulus. We also show that site-specific cleavage within the MLL bcr can be linked to the higher-order chromatin fragmentation that occurs during the initial stages of apoptosis, possibly through cleavage of DNA loops at their anchorage sites to the nuclear matrix. In addition, we show that site-specific cleavage is conserved between species, as specific DNA cleavage can also be demonstrated within the murine MLL locus. Lastly, site-specific cleavage during apoptosis can also be identified at the AML1 locus, a locus which is also frequently involved in chromosomal rearrangements present in t-AML patients. In conclusion, these results suggest the potential involvement of higher-order chromatin fragmentation which occurs as a part of a generalized apoptotic response in a mechanism leading to chromosomal translocation of the MLL and AML1 genes and subsequent t-AML.

scholarly journals Local base sequence preferences for DNA cleavage by mammalian topoisomerase II in the presence of amsacrine or teniposide

1991 ◽  
Vol 19 (24) ◽  
pp. 7003-7003 ◽  
Author(s):  
Y. Pommier ◽  
G. Capranico ◽  
A. Orr ◽  
K.W. Kohn
Keyword(s):  
Dna Cleavage ◽  
Topoisomerase Ii ◽  
Base Sequence ◽  
Local Base

scholarly journals Analysis of topoisomerase II-mediated DNA cleavage of the c-myc gene during HL60 differentiation

FEBS Letters ◽  
1993 ◽  
Vol 334 (3) ◽  
pp. 369-372 ◽  
Author(s):  
Jean-François Riou ◽  
Michèle Gabillot ◽  
Guy Riou
Keyword(s):  
Dna Cleavage ◽  
Topoisomerase Ii ◽  
Myc Gene

scholarly journals Drug Stimulated DNA Cleavage Mediated by Cauliflower Topoisomerase II

1991 ◽  
Vol 95 (2) ◽  
pp. 659-662 ◽  
Author(s):  
Boe S. Sørensen ◽  
Hideki Fukata ◽  
Palle S. Jensen ◽  
Anni H. Andersen ◽  
Kent Christiansen ◽  
...  
Keyword(s):  
Dna Cleavage ◽  
Topoisomerase Ii
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