Rif1 provides a new DNA-binding interface for the Bloom syndrome complex to maintain normal replication
Autor: | Keli Agama, Steven J. Brill, Parameswary A. Muniandy, Dongyi Xu, Michael M. Seidman, Miki, Rong Guo, Nan Ping Weng, Saravanabhavan Thangavel, Yves Pommier, Xi Shen, Amom Ruhikanta Meetei, Lei Li, Jinhu Yin, Huy Nguyen, Weidong Wang, Elisabetta Leo, Lauren E. Wilson, Alessandro Vindigni, David A. Fox |
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Jazyk: | angličtina |
Rok vydání: | 2010 |
Předmět: |
DNA Replication
congenital hereditary and neonatal diseases and abnormalities Multiprotein complex Blotting Western Molecular Sequence Data Telomere-Binding Proteins Kidney DNA-binding protein General Biochemistry Genetics and Molecular Biology Article Cell Line chemistry.chemical_compound medicine Holliday junction Animals Humans Immunoprecipitation Bloom syndrome Amino Acid Sequence RNA Small Interfering Molecular Biology Polymerase Genetics General Immunology and Microbiology biology RecQ Helicases Sequence Homology Amino Acid urogenital system General Neuroscience DNA replication Helicase nutritional and metabolic diseases Nuclear Proteins DNA medicine.disease Cell biology DNA-Binding Proteins chemistry biology.protein Carrier Proteins Chickens HeLa Cells |
Popis: | BLM, the helicase defective in Bloom syndrome, is part of a multiprotein complex that protects genome stability. Here, we show that Rif1 is a novel component of the BLM complex and works with BLM to promote recovery of stalled replication forks. First, Rif1 physically interacts with the BLM complex through a conserved C-terminal domain, and the stability of Rif1 depends on the presence of the BLM complex. Second, Rif1 and BLM are recruited with similar kinetics to stalled replication forks, and the Rif1 recruitment is delayed in BLM-deficient cells. Third, genetic analyses in vertebrate DT40 cells suggest that BLM and Rif1 work in a common pathway to resist replication stress and promote recovery of stalled forks. Importantly, vertebrate Rif1 contains a DNA-binding domain that resembles the αCTD domain of bacterial RNA polymerase α; and this domain preferentially binds fork and Holliday junction (HJ) DNA in vitro and is required for Rif1 to resist replication stress in vivo. Our data suggest that Rif1 provides a new DNA-binding interface for the BLM complex to restart stalled replication forks. |
Databáze: | OpenAIRE |
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