Analysis of a new genetic disorder caused by the deficiency in radiation-induced DNA double-strand break repair

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H05333
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: Nagasaki University
• Principal Investigator: NAKAZAWA Yuka 長崎大学, 原爆後障害医療研究所, 助教 (00533902)
• Research Collaborator: JEGGO Penny
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 修復 / DNA修復 / NHEJ / 遺伝性疾患

Outline of Final Research Achievements

We analyzed an uncharacterised Cockayne syndrome like patient with normal NER (nucleotide excision repair) activity. We performed next-generation exome sequencing and identified pathogenic mutations in the XRCC4 gene, which encodes a non-homologous end joining (NHEJ) protein required for the ligation process. Our XRCC4 syndrome patient retained normal immune response, although LIG4 syndrome patients usually display immunodeficiency. Fibroblast cell lines derived from the XRCC4 and LIG4 patients showed significant radiation sensitivity. We performed plasmid-based V(D)J recombination assays for the XRCC4 patient cell lines. We are currently establishing model mice to further study molecular pathogeneses of XRCC4 syndrome.

Free Research Field

DNA修復学、人類遺伝学