Results 1 to 10 of about 4,991 (120)

Selective small molecule PARG inhibitor causes replication fork stalling and cancer cell death [PDF]

Nature Communications, 2019
PARG catalyzes the removal of poly(ADP-ribose) (PAR) from target proteins and executes critical functions in the DNA damage response. Here the authors provide structural and biological insight with small molecule PARG inhibitors and show that PARG ...
Jerry H. Houl, Zu Ye, Chris A. Brosey, Lakshitha P. F. Balapiti-Modarage, Sarita Namjoshi, Albino Bacolla, Daniel Laverty, Brian L. Walker, Yasin Pourfarjam, Leslie S. Warden, Naga Babu Chinnam, Davide Moiani, Roderick A. Stegeman, Mei-Kuang Chen, Mien-Chie Hung, Zachary D. Nagel, Tom Ellenberger, In-Kwon Kim, Darin E. Jones, Zamal Ahmed, John A. Tainer   +20 more
doaj   +7 more sources

PARG inhibitor sensitivity correlates with accumulation of single-stranded DNA gaps in preclinical models of ovarian cancer [PDF]

Proceedings of the National Academy of Sciences of the United States of America
Poly (ADP-ribose) glycohydrolase (PARG) is a dePARylating enzyme which promotes DNA repair by removal of poly (ADP-ribose) (PAR) from PARylated proteins. Loss or inhibition of PARG results in replication stress and sensitizes cancer cells to DNA-damaging agents.
Ramya Ravindranathan, , Geoffrey I Shapiro   +2 more
exaly   +4 more sources

Prospects for PARG inhibitors in cancer therapy [PDF]

Journal of Molecular Cell Biology
Abstract Poly(ADP-ribose) glycosylhydrolase (PARG) is an enzyme involved in hydrolyzing the ribose–ribose bonds present in poly(ADP-ribose) (PAR), which are primarily found in the nucleus. Along with poly(ADP-ribose) polymerase, PARG regulates the level of PAR in cells, playing a crucial role in DNA maintenance and repair processes ...
Zu Ye, Ji Jing, Ye Zu
exaly   +4 more sources

Intrinsic PARG inhibitor sensitivity is mimicked by TIMELESS haploinsufficiency and rescued by nucleoside supplementation. [PDF]

NAR Cancer
Abstract A subset of cancer cells are intrinsically sensitive to inhibitors targeting PARG, the poly(ADP-ribose) glycohydrolase that degrades PAR chains. Sensitivity is accompanied by persistent DNA replication stress, and can be induced by inhibition of TIMELESS, a replisome accelerator.
Coulson-Gilmer C, Littler S, Barnes BM, Brady RM, Anagho HA, Pillay N, Dey M, Macmorland W, Bronder D, Nelson L, Tighe A, Lin WH, Morgan RD, Unwin RD, Nielsen ML, McGrail JC, Taylor SS.   +16 more
europepmc   +5 more sources

Loss‐of‐function genetic screen unveils synergistic efficacy of PARG inhibition with combined 5‐fluorouracil and irinotecan treatment in colorectal cancer [PDF]

Clinical and Translational Medicine
Background Colorectal cancer (CRC) remains a major global health concern, partly due to resistance to therapy and the lack of new effective treatments for advanced disease.
Cristina Queralt, Cristina Moreta‐Moraleda, Marta Costa, Ferran Grau‐Leal, Jeannine Diesch, Carla Vendrell‐Ayats, Eva Musulén, Roni H G Wright, Cristina Bugés, José Luis Manzano, Sara Cabrero‐de las Heras, Johannes Zuber, Marcus Buschbeck, Sonia‐V Forcales, Eva Martínez‐Balibrea   +14 more
doaj   +2 more sources

Selective Loss of PARG Restores PARylation and Counteracts PARP Inhibitor-Mediated Synthetic Lethality [PDF]

Cancer Cell, 2018
Inhibitors of poly(ADP-ribose) (PAR) polymerase (PARPi) have recently entered the clinic for the treatment of homologous recombination (HR)-deficient cancers. Despite the success of this approach, drug resistance is a clinical hurdle, and we poorly understand how cancer cells escape the deadly effects of PARPi without restoring the HR pathway.
Ewa Gogola, Wouter W Wiegant, Roebi de Bruijn   +2 more
exaly   +10 more sources

Synergistic Cellular Toxicity from Inhibition of Poly(ADP-ribose) Glycohydrolase (PARG) and Ubiquitin-Specific Protease 1 (USP1) [PDF]

Toxics
Ubiquitin-specific protease 1 (USP1) is an emerging target for poly(ADP-ribose) polymerase 1 (PARP1) inhibitor-resistant and BRCA1/BRCA2 mutant tumors.
Stefan M. Leonard, Charlotte R. Pearson, Wynand P. Roos, Robert W. Sobol   +3 more
doaj   +2 more sources

Anticancer sensitivities and biological characteristics of HCT116 cells resistant to the selective poly(ADP‐ribose) glycohydrolase inhibitor [PDF]

FEBS Open Bio
Poly(ADP‐ribose) glycohydrolase (PARG) is a key enzyme involved in poly(ADP‐ribose) (PAR) degradation and is considered a potential anticancer target. We previously investigated resistance mechanisms to the PARG inhibitor PDD00017273 in human colorectal ...
Kaede Tsuda, Yoko Ogino, Akira Sato
doaj   +2 more sources

PARG inhibition suppresses breast cancer progression and potentiates immunoresponse through MTDH degradation mediated by E3 ligase ITCH-dependent ubiquitination [PDF]

npj Breast Cancer
PARG plays an important role in cancer progression and immunoresponse, but its role in breast cancer is not yet fully elucidated. The advanced breast cancer is still a persistent challenge in clinical oncology.
Junnai Wang, Yanhua Dong, Weiwei Lun, Manman Nai, Yajing Shi, Jianfang Geng, Wenhui Cai, Jiaxi Liu, Hongyu Li, Lei Li   +9 more
doaj   +2 more sources

CHK1 inhibitor induced PARylation by targeting PARG causes excessive replication and metabolic stress and overcomes chemoresistance in ovarian cancer

Cell Death Discovery
Chemoresistance contributes to the majority of deaths in women with ovarian cancer (OC). Altered DNA repair and metabolic signaling is implicated in mediating therapeutic resistance.
Ganesh Acharya, Chinnadurai Mani, Naresh Sah, Karunakar Saamarthy, Robert Young, Mark B. Reedy, Robert W. Sobol, Komaraiah Palle   +7 more
doaj   +3 more sources