BCR/ABL regulates mammalian RecA homologs, resulting in drug resistance

Artur Slupianek; Christoph Schmutte; Gregory Tombline; Malgorzata Nieborowska-Skorska; Grażyna Hoser; Michal O. Nowicki; Andrew J. Pierce; Richard Fishel; Tomasz Skorski

doi:10.1016/S1097-2765(01)00357-4

BCR/ABL regulates mammalian RecA homologs, resulting in drug resistance

Artur Slupianek
, Christoph Schmutte
, Gregory Tombline
, Malgorzata Nieborowska-Skorska
, Grażyna Hoser
, Michal O. Nowicki
, Andrew J. Pierce
, Richard Fishel
, Tomasz Skorski

Fox Chase Cancer Center
Temple University
Great Poland Cancer Center
University of Medical Sciences Poznan
Thomas Jefferson University
College of Science and Technology
State Med. Ctr. of Indust. Medicine
Medical Centre for Postgraduate Education, Warsaw
University of Pennsylvania
Medical University of Warsaw
Zakład Cytologii K.
Ohio State University
Cornell University

Research output: Contribution to journal › Article › peer-review

282 Scopus citations

Abstract

RAD51 is one of six mitotic human homologs of the E. coli RecA protein (RAD51-Paralogs) that play a central role in homologous recombination and repair of DNA double-strand breaks (DSBs). Here we demonstrate that RAD51 is important for resistance to cisplatin and mitomycin C in cells expressing the BCR/ABL oncogenic tyrosine kinase. BCR/ABL significantly enhances the expression of RAD51 and several RAD51-Paralogs. RAD51 overexpression is mediated by a STAT5-dependent transcription as well as by inhibition of caspase-3-dependent cleavage. Phosphorylation of the RAD51 Tyr-315 residue by BCR/ABL appears essential for enhanced DSB repair and drug resistance. Induction of the mammalian RecA homologs establishes a unique mechanism for DNA damage resistance in mammalian cells transformed by an oncogenic tyrosine kinase.

Original language	English
Pages (from-to)	795-806
Number of pages	12
Journal	Molecular Cell
Volume	8
Issue number	4
DOIs	https://doi.org/10.1016/S1097-2765(01)00357-4
State	Published - 2001

Keywords

Antibiotics, Antineoplastic/pharmacology
Antineoplastic Agents/pharmacology
Apoptosis/drug effects
Bone Marrow Cells/drug effects
Caspase 3
Caspase Inhibitors
Caspases/metabolism
Cell Line
Cisplatin/pharmacology
DNA Repair/physiology
DNA-Binding Proteins/genetics
Drug Resistance/physiology
Enzyme Activation
Fusion Proteins, bcr-abl/genetics
Genes, Reporter/genetics
Humans
Interleukin-3/pharmacology
Microscopy, Fluorescence
Milk Proteins
Mitomycin/pharmacology
Phosphorylation
Rad51 Recombinase
Rec A Recombinases/genetics
STAT5 Transcription Factor
Trans-Activators/genetics
Transcriptional Activation

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10.1016/S1097-2765(01)00357-4

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title = "BCR/ABL regulates mammalian RecA homologs, resulting in drug resistance",

abstract = "RAD51 is one of six mitotic human homologs of the E. coli RecA protein (RAD51-Paralogs) that play a central role in homologous recombination and repair of DNA double-strand breaks (DSBs). Here we demonstrate that RAD51 is important for resistance to cisplatin and mitomycin C in cells expressing the BCR/ABL oncogenic tyrosine kinase. BCR/ABL significantly enhances the expression of RAD51 and several RAD51-Paralogs. RAD51 overexpression is mediated by a STAT5-dependent transcription as well as by inhibition of caspase-3-dependent cleavage. Phosphorylation of the RAD51 Tyr-315 residue by BCR/ABL appears essential for enhanced DSB repair and drug resistance. Induction of the mammalian RecA homologs establishes a unique mechanism for DNA damage resistance in mammalian cells transformed by an oncogenic tyrosine kinase.",

keywords = "Antibiotics, Antineoplastic/pharmacology, Antineoplastic Agents/pharmacology, Apoptosis/drug effects, Bone Marrow Cells/drug effects, Caspase 3, Caspase Inhibitors, Caspases/metabolism, Cell Line, Cisplatin/pharmacology, DNA Repair/physiology, DNA-Binding Proteins/genetics, Drug Resistance/physiology, Enzyme Activation, Fusion Proteins, bcr-abl/genetics, Genes, Reporter/genetics, Humans, Interleukin-3/pharmacology, Microscopy, Fluorescence, Milk Proteins, Mitomycin/pharmacology, Phosphorylation, Rad51 Recombinase, Rec A Recombinases/genetics, STAT5 Transcription Factor, Trans-Activators/genetics, Transcriptional Activation",

author = "Artur Slupianek and Christoph Schmutte and Gregory Tombline and Malgorzata Nieborowska-Skorska and Gra{\.z}yna Hoser and Nowicki, \{Michal O.\} and Pierce, \{Andrew J.\} and Richard Fishel and Tomasz Skorski",

year = "2001",

doi = "10.1016/S1097-2765(01)00357-4",

language = "English",

volume = "8",

pages = "795--806",

journal = "Molecular Cell",

issn = "1097-2765",

publisher = "Cell Press",

number = "4",

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TY - JOUR

T1 - BCR/ABL regulates mammalian RecA homologs, resulting in drug resistance

AU - Slupianek, Artur

AU - Schmutte, Christoph

AU - Tombline, Gregory

AU - Nieborowska-Skorska, Malgorzata

AU - Hoser, Grażyna

AU - Nowicki, Michal O.

AU - Pierce, Andrew J.

AU - Fishel, Richard

AU - Skorski, Tomasz

PY - 2001

Y1 - 2001

N2 - RAD51 is one of six mitotic human homologs of the E. coli RecA protein (RAD51-Paralogs) that play a central role in homologous recombination and repair of DNA double-strand breaks (DSBs). Here we demonstrate that RAD51 is important for resistance to cisplatin and mitomycin C in cells expressing the BCR/ABL oncogenic tyrosine kinase. BCR/ABL significantly enhances the expression of RAD51 and several RAD51-Paralogs. RAD51 overexpression is mediated by a STAT5-dependent transcription as well as by inhibition of caspase-3-dependent cleavage. Phosphorylation of the RAD51 Tyr-315 residue by BCR/ABL appears essential for enhanced DSB repair and drug resistance. Induction of the mammalian RecA homologs establishes a unique mechanism for DNA damage resistance in mammalian cells transformed by an oncogenic tyrosine kinase.

AB - RAD51 is one of six mitotic human homologs of the E. coli RecA protein (RAD51-Paralogs) that play a central role in homologous recombination and repair of DNA double-strand breaks (DSBs). Here we demonstrate that RAD51 is important for resistance to cisplatin and mitomycin C in cells expressing the BCR/ABL oncogenic tyrosine kinase. BCR/ABL significantly enhances the expression of RAD51 and several RAD51-Paralogs. RAD51 overexpression is mediated by a STAT5-dependent transcription as well as by inhibition of caspase-3-dependent cleavage. Phosphorylation of the RAD51 Tyr-315 residue by BCR/ABL appears essential for enhanced DSB repair and drug resistance. Induction of the mammalian RecA homologs establishes a unique mechanism for DNA damage resistance in mammalian cells transformed by an oncogenic tyrosine kinase.

KW - Antibiotics, Antineoplastic/pharmacology

KW - Antineoplastic Agents/pharmacology

KW - Apoptosis/drug effects

KW - Bone Marrow Cells/drug effects

KW - Caspase 3

KW - Caspase Inhibitors

KW - Caspases/metabolism

KW - Cell Line

KW - Cisplatin/pharmacology

KW - DNA Repair/physiology

KW - DNA-Binding Proteins/genetics

KW - Drug Resistance/physiology

KW - Enzyme Activation

KW - Fusion Proteins, bcr-abl/genetics

KW - Genes, Reporter/genetics

KW - Humans

KW - Interleukin-3/pharmacology

KW - Microscopy, Fluorescence

KW - Milk Proteins

KW - Mitomycin/pharmacology

KW - Phosphorylation

KW - Rad51 Recombinase

KW - Rec A Recombinases/genetics

KW - STAT5 Transcription Factor

KW - Trans-Activators/genetics

KW - Transcriptional Activation

UR - https://www.scopus.com/pages/publications/0034760095

U2 - 10.1016/S1097-2765(01)00357-4

DO - 10.1016/S1097-2765(01)00357-4

M3 - Article

C2 - 11684015

SN - 1097-2765

VL - 8

SP - 795

EP - 806

JO - Molecular Cell

JF - Molecular Cell

IS - 4

ER -

BCR/ABL regulates mammalian RecA homologs, resulting in drug resistance

Abstract

Keywords

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