JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M103962200 on June 13, 2001

J. Biol. Chem., Vol. 276, Issue 34, 31590-31595, August 24, 2001
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
276/34/31590    most recent
M103962200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sim, S.-P.
Right arrow Articles by Liu, L. F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sim, S.-P.
Right arrow Articles by Liu, L. F.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Nucleolytic Cleavage of the Mixed Lineage Leukemia Breakpoint Cluster Region during Apoptosis*

Sai-Peng SimDagger and Leroy F. LiuDagger §

From the Dagger  Department of Pharmacology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854 and the § Cancer Institute of New Jersey, New Brunswick, New Jersey 08901

VP-16 (etoposide) has recently been shown to induce topoisomerase II (TOP2)-mediated DNA cleavage within the mixed lineage leukemia (MLL) breakpoint cluster region (bcr), suggesting a role of TOP2 in MLL gene rearrangement. In our current studies, we have compared the induction of DNA cleavage within the MLL bcr in different cell lines after treatment with various anticancer drugs. All anticancer drugs tested including VP-16 (a TOP2-directed drug), camptothecin (a topoisomerase I-directed drug), 5-fluorouracil and methotrexate (antimetabolites), and vinblastine (a microtubule inhibitor) induced the same site-specific cleavage within the MLL bcr. This cleavage was shown to be nuclease-mediated but not TOP2-mediated by the following observations: 1) drug-induced cleavage within the MLL bcr was not protein-linked; 2) unlike TOP2-mediated cleavage, drug-induced DNA cleavage within the MLL bcr was kinetically slow and coincided with the formation of the apoptotic nucleosomal DNA ladder; 3) drug-induced cleavage within the MLL bcr was unaffected in cells with reduced nuclear TOP2; and 4) drug-induced cleavage within the MLL bcr was abolished by the caspase inhibitor, Z-Asp(OCH3)-Glu(OCH3)-Val-Asp(OCH3)-FMK. The possibility that an apoptotic nuclease may be involved in cleavage of the MLL bcr and MLL gene translocation is discussed.

* This work was supported by National Institutes of Health Grants GM27731 and CA39962.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Dept. of Pharmacology, UMDNJ-Robert Wood Johnson Medical School, 675 Hoes Ln., Piscataway, NJ 08854. Tel.: 732-235-4592; Fax: 732-235-4073; E-mail: lliu@umdnj.edu.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 BloodHome page
B. W. Robinson, N.-K. V. Cheung, C. P. Kolaris, S. C. Jhanwar, J. K. Choi, N. Osheroff, and C. A. Felix
Prospective tracing of MLL-FRYL clone with low MEIS1 expression from emergence during neuroblastoma treatment to diagnosis of myelodysplastic syndrome
Blood, April 1, 2008; 111(7): 3802 - 3812.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
A. M. Azarova, Y. L. Lyu, C.-P. Lin, Y.-C. Tsai, J. Y.-N. Lau, J. C. Wang, and L. F. Liu
From the Cover: Roles of DNA topoisomerase II isozymes in chemotherapy and secondary malignancies
PNAS, June 26, 2007; 104(26): 11014 - 11019.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
E. S. Hars, Y. L. Lyu, C.-P. Lin, and L. F. Liu
Role of Apoptotic Nuclease Caspase-Activated DNase in Etoposide-Induced Treatment-Related Acute Myelogenous Leukemia.
Cancer Res., September 15, 2006; 66(18): 8975 - 8979.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
Y. Otake, A. Mims, and D. J. Fernandes
Merbarone Induces Activation of Caspase-Activated DNase and Excision of Chromosomal DNA Loops from the Nuclear Matrix
Mol. Pharmacol., April 1, 2006; 69(4): 1477 - 1485.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
G. S. Boehden, A. Restle, R. Marschalek, C. Stocking, and L. Wiesmuller
Recombination at chromosomal sequences involved in leukaemogenic rearrangements is differentially regulated by p53
Carcinogenesis, August 1, 2004; 25(8): 1305 - 1313.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. Khobta, C. Carlo-Stella, and G. Capranico
Specific Histone Patterns and Acetylase/Deacetylase Activity at the Breakpoint-Cluster Region of the Human MLL Gene
Cancer Res., April 15, 2004; 64(8): 2656 - 2662.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.