2019 Fiscal Year Final Research Report
Analysis of S-phase specific replication coupled NER
| Project/Area Number |
16K08580
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
General medical chemistry
|
|---|
| Research Institution | Hamamatsu University School of Medicine |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2016-04-01 – 2020-03-31
|
| Keywords | 紫外線 / ヌクレオチド除去修復 / ヒストン / アセチル化 / 脱アセチル化 / HBO1 / HDAC3 |
|---|
| Outline of Final Research Achievements |
We analyzed a novel intracellular factor involved in nucleotide excision repair (NER) that repairs DNA damage after ultraviolet (UV) irradiation. As a result, it was demonstrated that histone acetyltransferase HBO1 acetylates histone H3K14 at the damage site to recruit chromatin remodeling factors of ISWI family and promote accumulation of NER core factors such as XPC. HBO1 phosphorylation in S phase was carried out by ATR that was activated during inhibition of DNA replication. On the other hand, interestingly, it was revealed that the histone deacetylase HDAC3, which deacetylates histone H3K14, also plays a role in recruitment to the damaged site of XPC.
|
| Free Research Field |
DNA損傷修復
|
| Academic Significance and Societal Importance of the Research Achievements |
様々なDNA損傷に働くNER機構が破綻するとメラノーマなど遺伝子変異の多い癌の原因となる。我々の研究から細胞内でNERが正常に働くためにクロマチン構造をオープンにするヒストン修飾と反対にクロマチンをクローズするヒストン修飾両方が必要とされることが示された。この結果はDNA修復過程においてダイナミックな染色体構造の変換が能動的に起こることを意味しており細胞内のNERを理解する一助となる。NERに必要な新たな因子をモニターすることで癌の早期発見など臨床的な応用も可能となる。
|
