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FANCD2 influences replication fork processes and genome stability in response to clustered DSBs

文献类型：期刊论文

作者Asaithamby, Aroumougame1; Zhu, Jiayun1; Su, Fengtao1; Mukherjee, Shibani3; Mori, Eiichiro1; Hu, Burong2
刊名CELL CYCLE
出版日期2015-06-18
卷号14页码:1809-1822
关键词clustered DSBs DNA replication FANCD2 genome instability high-LET radiation
ISSN号1538-4101
DOI10.1080/15384101.2015.1036210
英文摘要Fanconi Anemia (FA) is a cancer predisposition syndrome and the factors defective in FA are involved in DNA replication, DNA damage repair and tumor suppression. Here, we show that FANCD2 is critical for genome stability maintenance in response to high-linear energy transfer (LET) radiation. We found that FANCD2 is monoubiquitinated and recruited to the sites of clustered DNA double-stranded breaks (DSBs) specifically in S/G2 cells after high-LET radiation. Further, FANCD2 facilitated the repair of clustered DSBs in S/G2 cells and proper progression of S-phase. Furthermore, lack of FANCD2 led to a reduced rate of replication fork progression and elevated levels of both replication fork stalling and new origin firing in response to high-LET radiation. Mechanistically, FANCD2 is required for correct recruitment of RPA2 and Rad51 to the sites of clustered DSBs and that is critical for proper processing of clustered DSBs. Significantly, FANCD2-decifient cells exhibited defective chromosome segregation, elevated levels of chromosomal aberrations, and anchorage-independent growth in response to high-LET radiation. These findings establish FANCD2 as a key factor in genome stability maintenance in response to high-LET radiation and as a promising target to improve cancer therapy.
WOS关键词DOUBLE-STRAND BREAKS ; FANCONI-ANEMIA PATHWAY ; CROSS-LINK REPAIR ; INDUCE CHROMOSOME BREAKAGE ; MULTIPLY DAMAGED SITES ; DNA-END RESECTION ; HOMOLOGOUS RECOMBINATION ; HUMAN-CELLS ; MONOUBIQUITINATED FANCD2 ; IONIZING-RADIATION
资助项目National Aeronautics and Space Association[NNX13AD57G] ; National Aeronautics and Space Association[NNX11AC54G]
WOS研究方向Cell Biology
语种英语
WOS记录号WOS:000356374600011
出版者TAYLOR & FRANCIS INC
资助机构National Aeronautics and Space Association
源URL[http://119.78.100.186/handle/113462/39990]  
专题近代物理研究所_空间辐射生物研究室
通讯作者Asaithamby, Aroumougame
作者单位1.Dept Radiat Oncol, Dallas, TX 75390 USA
2.Chinese Acad Sci, Inst Modern Phys, Key Lab Heavy Ion Radiat Biol & Med, Dept Space Radiobiol, Lanzhou, Peoples R China
3.Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA
推荐引用方式
GB/T 7714		 Asaithamby, Aroumougame,Zhu, Jiayun,Su, Fengtao,et al. FANCD2 influences replication fork processes and genome stability in response to clustered DSBs[J]. CELL CYCLE,2015,14:1809-1822.
APA Asaithamby, Aroumougame,Zhu, Jiayun,Su, Fengtao,Mukherjee, Shibani,Mori, Eiichiro,&Hu, Burong.(2015).FANCD2 influences replication fork processes and genome stability in response to clustered DSBs.CELL CYCLE,14,1809-1822.
MLA Asaithamby, Aroumougame,et al."FANCD2 influences replication fork processes and genome stability in response to clustered DSBs".CELL CYCLE 14(2015):1809-1822.

入库方式： OAI收割

来源：近代物理研究所

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