Aag DNA Glycosylase Promotes Alkylation-Induced Tissue Damage Mediated by Parp1

DSpace/Manakin Repository

Aag DNA Glycosylase Promotes Alkylation-Induced Tissue Damage Mediated by Parp1

Citable link to this page


Title: Aag DNA Glycosylase Promotes Alkylation-Induced Tissue Damage Mediated by Parp1
Author: Calvo, Jennifer A.; Moroski-Erkul, Catherine A.; Lake, Annabelle; Eichinger, Lindsey W.; Shah, Dharini; Jhun, Iny; Limsirichai, Prajit; Bronson, Roderick Terry; Christiani, David C.; Meira, Lisiane B.; Samson, Leona D.

Note: Order does not necessarily reflect citation order of authors.

Citation: Calvo, Jennifer A., Catherine A. Moroski-Erkul, Annabelle Lake, Lindsey W. Eichinger, Dharini Shah, Iny Jhun, Prajit Limsirichai, et al. 2013. Aag dna glycosylase promotes alkylation-induced tissue damage mediated by parp1. PLoS Genetics 9(4): e1003413.
Full Text & Related Files:
Abstract: Alkylating agents comprise a major class of front-line cancer chemotherapeutic compounds, and while these agents effectively kill tumor cells, they also damage healthy tissues. Although base excision repair (BER) is essential in repairing DNA alkylation damage, under certain conditions, initiation of BER can be detrimental. Here we illustrate that the alkyladenine DNA glycosylase (AAG) mediates alkylation-induced tissue damage and whole-animal lethality following exposure to alkylating agents. Aag-dependent tissue damage, as observed in cerebellar granule cells, splenocytes, thymocytes, bone marrow cells, pancreatic β-cells, and retinal photoreceptor cells, was detected in wild-type mice, exacerbated in Aag transgenic mice, and completely suppressed in Aag−/− mice. Additional genetic experiments dissected the effects of modulating both BER and Parp1 on alkylation sensitivity in mice and determined that Aag acts upstream of Parp1 in alkylation-induced tissue damage; in fact, cytotoxicity in WT and Aag transgenic mice was abrogated in the absence of Parp1. These results provide in vivo evidence that Aag-initiated BER may play a critical role in determining the side-effects of alkylating agent chemotherapies and that Parp1 plays a crucial role in Aag-mediated tissue damage.
Published Version: doi:10.1371/journal.pgen.1003413
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3617098/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:11180413
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)


Search DASH

Advanced Search