involvement of INO80 chromatin remodeling factor in 11q23 chromosome translocations

2016 Fiscal Year Final Research Report

• Project/Area Number: 26430114
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Hiroshima University
• Principal Investigator: Sun Jiying 広島大学, 原爆放射線医科学研究所, 講師 (80397926)
• Co-Investigator(Renkei-kenkyūsha): HARATA MASAHIKO 東北大学, 農学研究科, 准教授 (70218642)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 染色体転座形成 / DNA repair

Outline of Final Research Achievements

Chromosome translocations induced by ionizing radiation and chemotherapeutic agents, has been shown to lead to malignant transformation. However, the mechanism of chromosome translocations is still unclear. Chromosome translocations involving the MLL gene on 11q23 are the most frequent chromosome abnormalities in secondary leukemias associated with chemotherapy employing etoposide. Dysfunction of ATM, a DNA damage signaling regulator, increases the incidence of 11q23 chromosome translocations. We showed that ATM deficiency results in the excessive binding of the DNA recombinase RAD51 at the translocation breakpoint cluster region (BCR) of MLL gene after etoposide exposure. In this study, we showed that a phosphorylated subunit of INO80 complex by ATM, plays an important role in the appropriate regulation of INO80 and RAD51 binding to the BCR of MLL gene and prevention of 11q23 chromosome translocations after etoposide treatment.

Free Research Field

分子細胞生物学