PMID:22110608

Citation	Yin, DT, Wang, Q, Chen, L, Liu, MY, Han, C, Yan, Q, Shen, R, He, G, Duan, W, Li, JJ, Wani, A and Gao, JX (2011) Germline stem cell gene PIWIL2 mediates DNA repair through relaxation of chromatin. PLoS ONE 6:e27154
Abstract	DNA damage response (DDR) is an intrinsic barrier of cell to tumorigenesis initiated by genotoxic agents. However, the mechanisms underlying the DDR are not completely understood despite of extensive investigation. Recently, we have reported that ectopic expression of germline stem cell gene PIWIL2 is associated with tumor stem cell development, although the underlying mechanisms are largely unknown. Here we show that PIWIL2 is required for the repair of DNA-damage induced by various types of genotoxic agents. Upon ultraviolet (UV) irradiation, silenced PIWIL2 gene in normal human fibroblasts was transiently activated after treatment with UV light. This activation was associated with DNA repair, because Piwil2-deficienct mouse embryonic fibroblasts (mili(-/-) MEFs) were defective in cyclobutane pyrimidine dimers (CPD) repair after UV treatment. As a result, the UV-treated mili(-/-) MEFs were more susceptible to apoptosis, as characterized by increased levels of DNA damage-associated apoptotic proteins, such as active caspase-3, cleaved Poly (ADP-ribose) polymerase (PARP) and Bik. The impaired DNA repair in the mili(-/-) MEFs was associated with the reductions of histone H3 acetylation and chromatin relaxation, although the DDR pathway downstream chromatin relaxation appeared not to be directly affected by Piwil2. Moreover, guanine-guanine (Pt-[GG]) and double strand break (DSB) repair were also defective in the mili(-/-) MEFs treated by genotoxic chemicals Cisplatin and ionizing radiation (IR), respectively. The results indicate that Piwil2 can mediate DNA repair through an axis of Piwil2 → histone acetylation → chromatin relaxation upstream DDR pathways. The findings reveal a new role for Piwil2 in DNA repair and suggest that Piwil2 may act as a gatekeeper against DNA damage-mediated tumorigenesis.
Links	PubMed PMC3217960 Online version:10.1371/journal.pone.0027154
Keywords	Acetylation/drug effects; Acetylation/radiation effects; Animals; Argonaute Proteins/deficiency; Argonaute Proteins/genetics; Cell Death/drug effects; Cell Death/genetics; Cell Death/radiation effects; Cell Line; Chromatin/drug effects; Chromatin/metabolism; Chromatin/radiation effects; Cisplatin/pharmacology; DNA Damage/genetics; DNA Repair/genetics; Histones/metabolism; Humans; Infrared Rays/adverse effects; Mice; Mice, Inbred C57BL; Stem Cells/metabolism; Ultraviolet Rays/adverse effects
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:PIWL2		GO:2000617: positive regulation of histone H3-K9 acetylation	ECO:0000314:		P		Fig 4C. Western blotting reveals that piwil2 upregulates H3K9 acetylation in mouse embryonic fibroblasts irradiated by UV light.	complete CACAO 6943
MOUSE:PIWL2		GO:0043971: histone H3-K18 acetylation	ECO:0000314:		P		Fig 4C. Western blotting reveals that piwil2 upregulates H3K18 acetylation in mouse embryonic fibroblasts irradiated by UV light.	complete CACAO 6944
MOUSE:PIWL2		GO:0071442: positive regulation of histone H3-K14 acetylation	ECO:0000315:		P		Fig 4C. Western blotting reveals that piwil2 upregulates H3K14 acetylation in mouse embryonic fibroblasts irradiated by UV light.	complete CACAO 7106
MOUSE:PIWL2	involved_in	GO:2000617: positive regulation of histone H3-K9 acetylation	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:PIWL2	involved_in	GO:0071442: positive regulation of histone H3-K14 acetylation	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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