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Published on: January 31, 2018
TRIM29 regulates the assembly of DNA repair proteins into damaged chromatin
Yasushi Masuda1, Hidehisa Takahashi1, Shigeo Sato2
1Department of Biochemistry, Hokkaido University Graduate School of Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido 060-8638, Japan.
Abstract:
Although DNA double-strand break (DSB) repair is mediated by numerous proteins accumulated at DSB sites, how DNA repair proteins are assembled into damaged chromatin has not been fully elucidated. Here we show that a member of the tripartite motif protein family, TRIM29, is a histone-binding protein responsible for DNA damage response (DDR). We found that TRIM29 interacts with BRCA1-associated surveillance complex, cohesion, DNA-PKcs and components of TIP60 complex. The dynamics of the TRIM29-containing complex on H2AX nucleosomes is coordinated by a cross-talk between histone modifications. TRIM29 binds to modified histone H3 and H4 tails in the context of nucleosomes. Furthermore, chromatin binding of TRIM29 is required for the phosphorylation of H2AX and cell viability in response to ionizing radiation. Our results suggest that TRIM29 functions as a scaffold protein to assemble DNA repair proteins into chromatin followed by efficient activation of DDR.
Insights
Tripartite motif protein 29 (TRIM29) acts as a scaffold protein, binding histones to assemble DNA repair proteins at double-strand break sites. This assembly is crucial for activating the DNA damage response and maintaining cell viability after radiation.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- DNA double-strand breaks (DSBs) trigger a complex DNA damage response (DDR).
- The precise mechanisms of DNA repair protein assembly at DSB sites within chromatin remain incompletely understood.
- Understanding chromatin dynamics during DDR is essential for comprehending cellular response to genotoxic stress.
Purpose of the Study:
- To elucidate the role of tripartite motif protein 29 (TRIM29) in the DNA damage response.
- To investigate how TRIM29 facilitates the assembly of DNA repair proteins onto damaged chromatin.
- To determine the functional significance of TRIM29 in activating DDR pathways.
Main Methods:
- Chromatin immunoprecipitation assays to assess protein binding.
- Co-immunoprecipitation to identify protein interactions.
- Western blotting to detect histone modifications like H2AX phosphorylation.
- Cell viability assays following ionizing radiation exposure.
Main Results:
- TRIM29 was identified as a histone-binding protein involved in the DDR.
- TRIM29 interacts with key DDR proteins including the BRCA1-associated surveillance complex, cohesion, DNA-PKcs, and TIP60 complex components.
- TRIM29 binding to chromatin is essential for H2AX phosphorylation and cell survival after ionizing radiation.
- TRIM29 dynamics on H2AX nucleosomes are regulated by crosstalk between histone modifications.
Conclusions:
- TRIM29 functions as a critical scaffold protein in the DDR.
- TRIM29 facilitates the recruitment and assembly of DNA repair machinery onto damaged chromatin.
- TRIM29 plays a vital role in activating the DDR pathway and ensuring genomic stability.
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