ZSCAN4 Interacts with PARP1 to Promote DNA Repair in Mouse Embryonic Stem Cells

Overview

Journal Cell Biosci

Publisher Biomed Central

Specialty Biology

Date 2023 Oct 24

PMID 37875990

Authors

Li-Kuang Tsai

Min Peng

Chia-Chun Chang

Luan Wen

Lin Liu

Xiubin Liang

Y Eugene Chen

Jie Xu

Li-Ying Sung

Affiliations

Soon will be listed here.

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.

Citing Articles

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