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

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

281 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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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 - http://www.scopus.com/inward/record.url?scp=0034760095&partnerID=8YFLogxK

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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