Analysis of disorders defective in the mechanisms for fork stabilization

2015 Fiscal Year Final Research Report

• Project Area: Functions of non-coding DNA region for genome integrity
• Project/Area Number: 23114010
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kyoto University
• Principal Investigator: Minoru Takata 京都大学, 放射線生物研究センター, 教授 (30281728)
• Co-Investigator(Renkei-kenkyūsha): Ishiai Masamichi 京都大学, 放射線生物研究センター, 准教授 (90298844) ; 勝木 陽子 京都大学, 放射線生物研究センター, 研究員 (00645377) ; 平 明日香 京都大学, 放射線生物研究センター, 研究員 (30772777)
• Project Period (FY): 2011-04-01 – 2016-03-31
• Keywords: 複製ストレス / ゲノム安定性 / ファンコニ貧血経路 / チェックポイント / DNA複製

Outline of Final Research Achievements

It has been known that there are chromosomal fragile sites such as common fragile sites (CFS) among non-coding DNA regions that are prone to break upon replication stress and are conserved throughout evolution. Therefore these fragile sites are supposed to have a critical function for sustaining life, but its exact role remains unknown. In this study, we focused on chromatin dynamics at the fragile sites and the mechanisms of checkpoint signaling that stabilizes stalled replication forks. In particular, we analyzed (1) genome wide distribution of a key Fanconi anemia factor FANCD2 upon replication stress, (2) mechanisms of fork stabilization and breakage by proteomics analysis, (3) activation mechanisms of ATR-ATRIP replication checkpoint kinase.

Free Research Field

分子生物学、放射線分子生物学