ZSCAN4 interacts with PARP1 to promote DNA repair in mouse embryonic stem cells.
Journal
Cell & bioscience
Journal Volume
13
Journal Issue
1
Start Page
193
ISSN
2045-3701
Date Issued
2023-10-24
Author(s)
Tsai, Li-Kuang
Peng, Min
Wen, Luan
Liu, Lin
Liang, Xiubin
Chen, Y Eugene
Xu, Jie
Abstract
Background: In eukaryotic cells, DNA double strand breaks (DSB) are primarily repaired by canonical non-homologous end joining (c-NHEJ), homologous recombination (HR) and alternative NHEJ (alt-NHEJ). Zinc finger and SCAN domain containing 4 (ZSCAN4), sporadically expressed in 1–5% mouse embryonic stem cells (mESCs), is known to regulate genome stability by promoting HR. Results: Here we show that ZSCAN4 promotes DNA repair by acting with Poly (ADP-ribose) polymerase 1 (PARP1), which is a key member of the alt-NHEJ pathway. In the presence of PARP1, ZSCAN4-expressing mESCs are associated with lower extent of endogenous or chemical induced DSB comparing to ZSCAN4-negative ones. Reduced DSBs associated with ZSCAN4 are abolished by PARP1 inhibition, achieved either through small molecule inhibitor or gene knockout in mESCs. Furthermore, PARP1 binds directly to ZSCAN4, and the second ⍺-helix and the fourth zinc finger motif of ZSCAN4 are critical for this binding. Conclusions: These data reveal that PARP1 and ZSCAN4 have a protein–protein interaction, and shed light on the molecular mechanisms by which ZSCAN4 reduces DSB in mESCs. © 2023, Society of Chinese Bioscientists in America (SCBA).
Subjects
DNA double strand breaks
Mouse embryonic stem cells
PARP1
ZSCAN4
SDGs
Description
Article number: 193
Type
journal article