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

被引：262

作者：

Slupianek, A

Schmutte, C

Tombline, G

Nieborowska-Skorska, M

Hoser, G

Nowicki, MO

Pierce, AJ

Fishel, R ^{[1
]}

Skorski, T

机构：

[1] Temple Univ, Coll Sci & Technol, Ctr Biotechnol, Philadelphia, PA 19122 USA

[2] Thomas Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA 19107 USA

[3] Med Ctr Postgrad Educ, Warsaw, Poland

[4] Cornell Univ, Grad Sch Med Sci, Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA

来源：

MOLECULAR CELL | 2001年 / 8卷 / 04期

关键词：

D O I：

10.1016/S1097-2765(01)00357-4

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：795 / 806

页数：12

共 45 条

[1] Bcr-Abl exerts its antiapoptotic effect against diverse apoptotic stimuli through blockage of mitochondrial release of cytochrome c and activation of caspase-3 [J].