<?xml version='1.0' encoding='UTF-8'?><xml><records><record><source-app name="HighWire" version="7.x">Drupal-HighWire</source-app><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">KUNIHISA, TOMONARI</style></author><author><style face="normal" font="default" size="100%">INUBUSHI, SACHIKO</style></author><author><style face="normal" font="default" size="100%">TANINO, HIROKAZU</style></author><author><style face="normal" font="default" size="100%">HOFFMAN, ROBERT M.</style></author></authors><secondary-authors></secondary-authors></contributors><titles><title><style face="normal" font="default" size="100%">Induction of the DNA-Repair Gene POLQ only in BRCA1-mutant Breast-Cancer Cells by Methionine Restriction</style></title><secondary-title><style face="normal" font="default" size="100%">Cancer Genomics - Proteomics</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2024</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2024-07-01 00:00:00</style></date></pub-dates></dates><pages><style  face="normal" font="default" size="100%">399-404</style></pages><doi><style  face="normal" font="default" size="100%">10.21873/cgp.20458</style></doi><volume><style face="normal" font="default" size="100%">21</style></volume><issue><style face="normal" font="default" size="100%">4</style></issue><abstract><style  face="normal" font="default" size="100%">Background/Aim: BRCA1/2 mutations in breast cancer cells impair homologous recombination and promote alternative end joining (Alt-EJ) for DNA-damage repair. DNA polymerase theta, encoded by POLQ, plays a crucial role in Alt-EJ, making it a potential therapeutic target, particularly in BRCA1/2-mutant cancers. Methionine restriction is a promising approach to target cancer cells due to their addiction to this amino acid. The present study investigated the expression of POLQ in BRCA1/2 wild-type and BRCA1-mutant breast cancer cells under methionine restriction. Materials and Methods: POLQ mRNA expression was measured using qRT-PCR in BRCA1/2 wild-type (MDA-MB-231) and BRCA1- mutant (HCC1937 and MDA-MB-436) breast-cancer cells under normal, or serum-restricted, or serum- and methionine-restricted conditions. Results: Compared to BRCA1/2 wild-type cells, BRCA1-mutant cells displayed significantly higher basal POLQ expression in normal medium. Methionine restriction further increased POLQ expression in the BRCA1-mutant cells but decreased it in the BRCA1/2 wild-type cells. Conclusion: The present findings suggest that methionine restriction showed differential effects on POLQ expression, potentially impacting Alt-EJ activity, in BRCA1/2 wild-type and BRCA1-mutant breast-cancer cells. Further investigation is needed to explore the potential of combining methionine restriction with DNA-repair inhibitors, such as PARP inhibitors, to overcome drug resistance in BRCA1/2 mutant cancers.</style></abstract></record></records></xml>