Single strand DNA binding proteins 1 and 2 protect newly replicated telomeres  

作　　者：Peili Gu Wei Deng Ming Lei Sandy Chang 

机构地区：[1]Department of Laboratory Medicine and Pathology, Yale University School of Medicine, 330 Cedar St., New Haven, CT 06520, USA [2]State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China [3]National Center for Protein Science Shang- hai, 320 Yueyang Road, Shanghai 200031, China

出　　处：《Cell Research》2013年第5期705-719,共15页细胞研究（英文版）

摘　　要：Human single-strand （ss） DNA binding proteins 1 and 2 （hSSB1 and 2） are components of the hSSB1/2-INTS3- C9orf80 heterotrimeric protein complex shown to participate in DNA damage response and maintenance of genome stability. However, their roles at telomeres remain unknown. Here, we generated murine SSB1 conditional knockout mice and cells and found that mSSB1 plays a critical role in telomere end protection. Both mSSB1 and mSSB2 lo- calize to a subset of telomeres and are required to repair TRF2-deficient telomeres. Deletion of mSSB1 resulted in increased chromatid-type fusions involving both leadingand lagging-strand telomeric DNA, suggesting that it is required for the protection of G-overhangs. mSSBI＇s interaction with INTS3 is required for its localization to damaged DNA. mSSB1 interacts with Potla, but not Potlb, and its association with telomeric ssDNA requires Potla. mSSBmice die at birth with developmental abnormalities, while mice with the hypomorphic mSSB1F/F allele are born alive and display increased sensitivity to ionizing radiation （IR）. Our results suggest that mSSB1 is required to maintain genome stability, and document a previously unrecognized role for mSSB1/2 in the protection of newly replicated leadingand lagging-strand telomeres.Human single-strand （ss） DNA binding proteins 1 and 2 （hSSB1 and 2） are components of the hSSB1/2-INTS3- C9orf80 heterotrimeric protein complex shown to participate in DNA damage response and maintenance of genome stability. However, their roles at telomeres remain unknown. Here, we generated murine SSB1 conditional knockout mice and cells and found that mSSB1 plays a critical role in telomere end protection. Both mSSB1 and mSSB2 lo- calize to a subset of telomeres and are required to repair TRF2-deficient telomeres. Deletion of mSSB1 resulted in increased chromatid-type fusions involving both leadingand lagging-strand telomeric DNA, suggesting that it is required for the protection of G-overhangs. mSSBI＇s interaction with INTS3 is required for its localization to damaged DNA. mSSB1 interacts with Potla, but not Potlb, and its association with telomeric ssDNA requires Potla. mSSBmice die at birth with developmental abnormalities, while mice with the hypomorphic mSSB1F/F allele are born alive and display increased sensitivity to ionizing radiation （IR）. Our results suggest that mSSB1 is required to maintain genome stability, and document a previously unrecognized role for mSSB1/2 in the protection of newly replicated leadingand lagging-strand telomeres.

关 键 词：TELOMERE DNA damage and repair cancer APOPTOSIS 

分 类 号：Q513.1[生物学—生物化学] S831.2[农业科学—畜牧学]