NDLI: Parp1 activation in mouse embryonic fibroblasts promotes Pol beta-dependent cellular hypersensitivity to alkylation damage.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Jelezcova, Elena Trivedi, Ram N. Wang, Xiao-Hong Tang, Jiang-Bo Brown, Ashley R. Goellner, Eva M. Schamus, Sandy Fornsaglio, Jamie L. Sobol, Robert W.
Description	Country affiliation: United States Author Affiliation: Jelezcova E ( Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine & University of Pittsburgh Cancer Institute, Hillman Cancer Center, Pittsburgh, PA 15213, USA.)
Abstract	Alkylating agents induce cell death in wild-type (WT) mouse embryonic fibroblasts (MEFs) by multiple mechanisms, including apoptosis, autophagy and necrosis. DNA polymerase beta (Pol beta) knockout (KO) MEFs are hypersensitive to the cytotoxic effect of alkylating agents, as compared to WT MEFs. To test the hypothesis that Parp1 is preferentially activated by methyl methanesulfonate (MMS) exposure of Pol beta KO MEFs, we have examined the relationship between Pol beta expression, Parp1 activation and cell survival following MMS exposure in a series of WT and Pol beta deficient MEF cell lines. Consistent with our hypothesis, we observed elevated Parp1 activation in Pol beta KO MEFs as compared to matched WT MEFs. Both the MMS-induced activation of Parp1 and the MMS-induced cytotoxicity of Pol beta KO MEFs are attenuated by pre-treatment with the Parp1/Parp2 inhibitor PJ34. Further, elevated Parp1 activation is observed following knockdown (KD) of endogenous Pol beta, as compared to WT cells. Pol beta KD MEFs are hypersensitive to MMS and both the MMS-induced hypersensitivity and Parp1 activation is prevented by pre-treatment with PJ34. In addition, the MMS-induced cellular sensitivity of Pol beta KO MEFs is reversed when Parp1 is also deleted (Pol beta/Parp1 double KO MEFs) and we observe no MMS sensitivity differential between Pol beta/Parp1 double KO MEFs and those that express recombinant mouse Pol beta. These studies suggest that Parp1 may function as a sensor of BER to initiate cell death when BER is aborted or fails. Parp1 may therefore function in BER as a tumor suppressor by initiating cell death and preventing the accumulation of cells with chromosomal damage due to a BER defect.
File Format	HTM / HTML
ISSN	13835718
e-ISSN	18793592
DOI	10.1016/j.mrfmmm.2010.01.016
Journal	Mutation Research/Genetic Toxicology and Environmental Mutagenesis
Issue Number	1-2
Volume Number	686
Language	English
Publisher	Elsevier
Publisher Date	2010-04-01
Publisher Place	Netherlands
Access Restriction	Open
Subject Keyword	Research Support, N.i.h., Extramural Cell Line Research Support, Non-u.s. Gov't Dna Repair Discipline Genetics Embryo, Mammalian Discipline Biochemistry Poly(adp-ribose) Polymerases Metabolism Alkylation Dna Damage Mice, Knockout Dna Polymerase Beta Animals Cell Death Up-regulation Fibroblasts Mice
Content Type	Text
Resource Type	Article
Subject	Genetics Health, Toxicology and Mutagenesis

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Base excision repair.

Poly(ADP-ribose) polymerase in the cellular response to DNA damage, apoptosis, and disease.

PARP inhibition: PARP1 and beyond.

Misregulation of gene expression in primary fibroblasts lacking poly(ADP-ribose) polymerase.

Role of poly(ADP-ribose) polymerase-1 in the removal of UV-induced DNA lesions by nucleotide excision repair.

Phenotypic characterization of Parp-1 and Parp-2 deficient mice and cells.

Poly(ADP-ribose) polymerase 1 regulates activity of DNA polymerase beta in long patch base excision repair.

Requirement of poly(ADP-ribose) polymerase in recovery from DNA damage in mice and in cells.

PARP1 promotes nucleotide excision repair through DDB2 stabilization and recruitment of ALC1

Parp1 activation in mouse embryonic fibroblasts promotes Pol beta-dependent cellular hypersensitivity to alkylation damage.

Similar Documents

Base excision repair.

Poly(ADP-ribose) polymerase in the cellular response to DNA damage, apoptosis, and disease.

PARP inhibition: PARP1 and beyond.

Misregulation of gene expression in primary fibroblasts lacking poly(ADP-ribose) polymerase.

Role of poly(ADP-ribose) polymerase-1 in the removal of UV-induced DNA lesions by nucleotide excision repair.

Phenotypic characterization of Parp-1 and Parp-2 deficient mice and cells.

Poly(ADP-ribose) polymerase 1 regulates activity of DNA polymerase beta in long patch base excision repair.

Requirement of poly(ADP-ribose) polymerase in recovery from DNA damage in mice and in cells.

PARP1 promotes nucleotide excision repair through DDB2 stabilization and recruitment of ALC1

Parp1 activation in mouse embryonic fibroblasts promotes Pol beta-dependent cellular hypersensitivity to alkylation damage.