Abstract:
:Histone methyltransferase G9a has critical roles in promoting cancer-cell growth and gene suppression, but whether it is also associated with the DNA damage response is rarely studied. Here, we report that loss of G9a impairs DNA damage repair and enhances the sensitivity of cancer cells to radiation and chemotherapeutics. In response to DNA double-strand breaks (DSBs), G9a is phosphorylated at serine 211 by casein kinase 2 (CK2) and recruited to chromatin. The chromatin-enriched G9a can then directly interact with replication protein A (RPA) and promote loading of the RPA and Rad51 recombinase to DSBs. This mechanism facilitates homologous recombination (HR) and cell survival. We confirmed the interaction between RPA and G9a to be critical for RPA foci formation and HR upon DNA damage. Collectively, our findings demonstrate a regulatory pathway based on CK2-G9a-RPA that permits HR in cancer cells and provide further rationale for the use of G9a inhibitors as a cancer therapeutic.
journal_name
Proc Natl Acad Sci U S Aauthors
Yang Q,Zhu Q,Lu X,Du Y,Cao L,Shen C,Hou T,Li M,Li Z,Liu C,Wu D,Xu X,Wang L,Wang H,Zhao Y,Yang Y,Zhu WGdoi
10.1073/pnas.1700694114subject
Has Abstractpub_date
2017-07-25 00:00:00pages
E6054-E6063issue
30eissn
0027-8424issn
1091-6490pii
1700694114journal_volume
114pub_type
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