KU70 Binding Protein 5 (KUB5), A Novel Factor in DNA Double Strand Break Repair and Radio-Resistance in Human Breast Cancer

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Title: KU70 Binding Protein 5 (KUB5), A Novel Factor in DNA Double Strand Break Repair and Radio-Resistance in Human Breast Cancer
Author: Rommel, Amy Ann
Abstract: DNA double strand breaks (DSBs ) are considered both mutagenic and carcinogenic if left un -repaired resulting in genomic instability and ultimately cancer . There are two main pathways for DSB repair : homologous recombination (HR ) and non -homologous end joining (NHEJ ) . Defects in DSB repair have already been associated with breast cancer formation and increased breast cancer risk . Breast cancer susceptibility genes , BRCA1 and BRCA2 are largely thought to be involved with HR while LIG4 , XRCC4 , and Ku70 are linked to NHEJ . Deficiencies in any one of these genes can predispose individuals to breast cancer . In addition to predisposition to breast cancer , altered DNA repair processes can influence chemo - and radiotherapy efficacy by creating resistance to therapy . To study NHEJ further , our laboratory has identified a novel Ku70 binding protein #5 (KUB5 ) by a yeast two -hybrid screen using Ku70 as bait . Loss of RTT103 , a putative yeast homolog of KUB5 , resulted in increased sensitivity to IR , similar to that observed in hdf1 -deletion yeast , the yeast homolog of Ku70 . Results also show that RTT103 -deletion yeast are deficient in repairing blunt and non -compatible DNA ends and re -expression of hKub5 can correct the IR -sensitivity and DNA repair deficiency of these deficient yeast demonstrating a strong functional model for human KUB5 function in yeast . Analyses of breast cancer cell lines for their KUB5 protein expression yielded a strong correlation between KUB5 protein level and sensitivity to DNA damage . These data strongly suggests that KUB5 is a novel repair factor involved in NHEJ and endogenous over -expression of KUB5 plays a role in chemotherapeutic and /or radio -therapeutic resistance via increasing the capacity to facilitate NHEJ repair of DSBs in breast cancer cells .
URI: http : / /hdl .handle .net /2152 .5 /865
Date: 2011-02-01

Citation

KU70 Binding Protein 5 (KUB5), A Novel Factor in DNA Double Strand Break Repair and Radio-Resistance in Human Breast Cancer. Graduate School of Biomedical Sciences. Available electronically from http : / /hdl .handle .net /2152 .5 /865 .

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