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Publication : Stella preserves maternal chromosome integrity by inhibiting 5hmC-induced γH2AX accumulation.

First Author  Nakatani T Year  2015
Journal  EMBO Rep Volume  16
Issue  5 Pages  582-9
PubMed ID  25694116 Mgi Jnum  J:222880
Mgi Id  MGI:5645854 Doi  10.15252/embr.201439427
Citation  Nakatani T, et al. (2015) Stella preserves maternal chromosome integrity by inhibiting 5hmC-induced gammaH2AX accumulation. EMBO Rep 16(5):582-9
abstractText  In the mouse zygote, Stella/PGC7 protects 5-methylcytosine (5mC) of the maternal genome from Tet3-mediated oxidation to 5-hydroxymethylcytosine (5hmC). Although ablation of Stella causes early embryonic lethality, the underlying molecular mechanisms remain unknown. In this study, we report impaired DNA replication and abnormal chromosome segregation (ACS) of maternal chromosomes in Stella-null embryos. In addition, phosphorylation of H2AX (gammaH2AX), which has been reported to inhibit DNA replication, accumulates in the maternal chromatin of Stella-null zygotes in a Tet3-dependent manner. Cell culture assays verified that ectopic appearance of 5hmC induces abnormal accumulation of gammaH2AX and subsequent growth retardation. Thus, Stella protects maternal chromosomes from aberrant epigenetic modifications to ensure early embryogenesis.
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