Title: The role of specific PP2A complexes in the dephosphorylation of γ-H2AX
Authors: Chen, Liping ×
Lai, Yandong
Zhu, Xiaonian
Ma, Lu
Bai, Qing
Vazquez, Iria
Xiao, Yongmei
Liu, Caixia
Li, Daochuan
Gao, Chen
He, Zhini
Zeng, Xiaowen
Xing, Xiumei
Zhang, Zhengbao
Li, Jie
Zhang, Bo
Wang, Qing
Sablina, Anna
Hahn, William C
Chen, Wenbo #
Issue Date: Jan-2015
Publisher: Co. of Biologists
Series Title: Journal of Cell Science vol:128 issue:2 pages:421
Article number: jcs.147223
Abstract: The formation of γ-H2AX in response to DNA double-strand breaks (DSBs) marks damaged regions for recognition and repair. Dephosphorylation of γ-H2AX is required for cells to resume cell cycle. However, the mechanisms of γ-H2AX dephosphorylation remain underexplored. Using a loss of function screen, we identified PP2A specific subunits, B56ε and α4, involved in elimination of γ-H2AX during DSBs repair process. In the early stage of DSBs repair the inhibitory subunit α4 binds and renders PP2Ac inactive. As DNA is repaired, α4 releases PP2Ac and triggers the assembly of an active PP2A B56ε holoenzyme. PP2A B56ε, which translocates from cytoplasm into the nucleus upon DNA damage, is responsible for a direct dephosphorylation of γ-H2AX. Suppression of both B56ε and α4 leads to persistence of γ-H2AX and defects in DNA repair. In contrast, the rapid clearance of γ-H2AX in human hepatocarcinoma is correlated with the over-expression of both B56ε and α4. Functional analysis reveals that PP2A B56ε coordinates with α4 in accelerating HR repair upon DNA damage. Together, these observations gain insight of how γ-H2AX dephosphorylation is kinetically regulated during DNA repair response.
ISSN: 0021-9533
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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