DNA replication-dependent/independent mechanism of gross chromosomal rearrangement

2014 Fiscal Year Final Research Report

• Project/Area Number: 24390085
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Human genetics
• Research Institution: Fujita Health University
• Principal Investigator: KURAHASHI Hiroki 藤田保健衛生大学, 総合医科学研究所, 教授 (30243215)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: FoSTeS / 染色体構造異常 / DNA複製 / 切断点 / 複製のストール / マイクロホモロジー / パリンドローム / 十字架型DNA

Outline of Final Research Achievements

We examined the mechanism of palindrome-mediated t(11;22) translocation using plasmid-based assay. Even in the plasmid lacking the replication origin showed translocation when transfected into the human cell line, suggesting that the t(11;22) translocation mechanism is independent of the DNA replication-based mechanism such as FoSTeS. On the other hand, we also examined breakpoints of three non-palindrome gross chromosomal rearrangement. One interstitial deletion and one duplication showed microhomology at the junction, suggesting the rearrangement took place via FoSTeS. In the third deletion case, we identified 11-13 nucleotide sequence at the upstream breakpoint that was repeated four times at the deletion junction. The backward replication slippage or serial replication slippage is the predicted mechanism. These data suggests that the aberrant DNA replication is involved in the generation of a major subset of deletion/duplication.

Free Research Field

細胞遺伝学