@article{c18a31b7275141698b770be53db3dd34,
title = "Loss of CHD1 causes DNA repair defects and enhances prostate cancer therapeutic responsiveness",
abstract = "The CHD1 gene, encoding the chromo-domain helicase DNA-binding protein-1, is one of the most frequently deleted genes in prostate cancer. Here, we examined the role of CHD1 in DNA double-strand break (DSB) repair in prostate cancer cells. We show that CHD1 is required for the recruitment of CtIP to chromatin and subsequent end resection during DNA DSB repair. Our data support a role for CHD1 in opening the chromatin around the DSB to facilitate the recruitment of homologous recombination (HR) proteins. Consequently, depletion of CHD1 specifically affects HR-mediated DNA repair but not non-homologous end joining. Together, we provide evidence for a previously unknown role of CHD1 in DNA DSB repair via HR and show that CHD1 depletion sensitizes cells to PARP inhibitors, which has potential therapeutic relevance. Our findings suggest that CHD1 deletion, like BRCA1/2 mutation in ovarian cancer, may serve as a marker for prostate cancer patient stratification and the utilization of targeted therapies such as PARP inhibitors, which specifically target tumors with HR defects.",
keywords = "CHD1, DNA repair, PARP inhibitor, chromatin, prostate cancer",
author = "Vijayalakshmi Kari and Mansour, {Wael Yassin} and Raul, {Sanjay Kumar} and Baumgart, {Simon J.} and Andreas Mund and Marian Grade and H{\"u}seyin Sirma and Ronald Simon and Hans Will and Matthias Dobbelstein and Ekkehard Dikomey and Johnsen, {Steven A.}",
note = "Funding Information: The authors would like to acknowledge R. Reimer (Microscope and Imaging facility, HPI, Hamburg) for help with the confocal fluorescence microscopy, G. Legube for providing AsiSI-U2OS cells, and S. Bolte and N. Molitor for technical support. A.M. is supported by a Marie Curie Intra-European Fellowship for Career Development (Project #627187). S.K.R. is supported by a National Overseas Scholarship, Government of India (11015/49/2010-SCD-V). This work was funded by the Deutsche Forschungsgemeinschaft (GRK1034) to S.A.J. Funding Information: The authors would like to acknowledge R. Reimer (Microscope and Imaging facility, HPI, Hamburg) for help with the confocal fluorescence microscopy, G. Legube for providing AsiSI-U2OS cells, and S. Bolte and N. Molitor for technical support. A.M. is supported by a Marie Curie Intra-European Fellowship for Career Development (Project #627187). S.K.R. is supported by a National Overseas Scholarship, Government of India (11015/49/2010-SCD-V). This work was funded by the Deutsche Forschungsgemeinschaft (GRK1034) to S.A.J.. Publisher Copyright: {\textcopyright} 2016 The Authors",
year = "2016",
month = nov,
day = "1",
doi = "10.15252/embr.201642352",
language = "English (US)",
volume = "17",
pages = "1609--1623",
journal = "EMBO Reports",
issn = "1469-221X",
publisher = "Nature Publishing Group",
number = "11",
}