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Rif1 provides a new DNA‐binding interface for the Bloom syndrome complex to maintain normal replication
Author(s) -
Xu Dongyi,
Muniandy Parameswary,
Leo Elisabetta,
Yin Jinhu,
Thangavel Saravanabhavan,
Shen Xi,
Ii Miki,
Agama Keli,
Guo Rong,
Fox David,
Meetei Amom Ruhikanta,
Wilson Lauren,
Nguyen Huy,
Weng Nanping,
Brill Steven J,
Li Lei,
Vindigni Alessandro,
Pommier Yves,
Seidman Michael,
Wang Weidong
Publication year - 2010
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2010.186
Subject(s) - biology , bloom syndrome , holliday junction , minichromosome maintenance , helicase , microbiology and biotechnology , dna replication , replication protein a , dna , genetics , dna repair , control of chromosome duplication , dna binding protein , rna , gene , transcription factor
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.