AI Article Synopsis
- Histone H2AX has a phosphorylation switch crucial for the DNA damage response, transitioning from pTyr142 to pSer139, with its specific functions still being studied.
- Research indicates that the constantly present H2AX-pY142, influenced by the WSTF protein, interacts with RNA polymerase II, promoting active transcription in cells that are dividing.
- The removal of H2AX-pY142 by certain phosphatases halts this interaction, causing transcriptional silencing at damaged DNA sites, while its reintroduction helps facilitate a specific type of DNA repair using active RNA transcripts as templates, thereby supporting genome stability.
Article Abstract
Histone H2AX undergoes a phosphorylation switch from pTyr142 (H2AX-pY142) to pSer139 (γH2AX) 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.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6614800 | PMC |
| http://dx.doi.org/10.1093/nar/gkz309 | DOI Listing |
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