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De novo phosphorylation of H2AX by WSTF regulates transcription-coupled homologous recombination repair

Authors
Ji, JH  | Min, S  | Chae, S | Ha, GH | Kim, Y | Park, YJ | Lee, CW | Cho, H
Citation
Nucleic acids research, 47(12). : 6299-6314, 2019
Journal Title
Nucleic acids research
ISSN
0305-10481362-4962
Abstract
Histone H2AX undergoes a phosphorylation switch from pTyr142 (H2AX-pY142) to pSer139 (gammaH2AX) in the DNA damage response (DDR): however, the functional role of H2AX-pY142 remains elusive. Here, we report a new layer of regulation involving transcription-coupled H2AX-pY142 in the DDR. We found that constitutive H2AX-pY142 generated by Williams-Beuren syndrome transcription factor (WSTF) interacts with RNA polymerase II (RNAPII) and is associated with RNAPII-mediated active transcription in proliferating cells. Also, removal of pre-existing H2AX-pY142 by ATM-dependent EYA1/3 phosphatases disrupts this association and requires for transcriptional silencing at transcribed active damage sites. The following recovery of H2AX-pY142 via translocation of WSTF to DNA lesions facilitates transcription-coupled homologous recombination (TC-HR) in the G1 phase, whereby RAD51 loading, but not RPA32, utilizes RNAPII-dependent active RNA transcripts as donor templates. We propose that the WSTF-H2AX-RNAPII axis regulates transcription and TC-HR repair to maintain genome integrity.
MeSH

DOI
10.1093/nar/gkz309
PMID
31045206
Appears in Collections:
Journal Papers > Research Organization > Genomic Instability Research Center
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
Ajou Authors
민, 선우  |  조, 혜성  |  지, 재훈
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