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Rif1 provides a new DNA-binding interface for the Bloom syndrome complex to maintain normal replication.

Abstract
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.
AuthorsDongyi Xu, Parameswary Muniandy, Elisabetta Leo, Jinhu Yin, Saravanabhavan Thangavel, Xi Shen, Miki Ii, Keli Agama, Rong Guo, David Fox 3rd, Amom Ruhikanta Meetei, Lauren Wilson, Huy Nguyen, Nan-ping Weng, Steven J Brill, Lei Li, Alessandro Vindigni, Yves Pommier, Michael Seidman, Weidong Wang
JournalThe EMBO journal (EMBO J) Vol. 29 Issue 18 Pg. 3140-55 (Sep 15 2010) ISSN: 1460-2075 [Electronic] England
PMID20711169 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Carrier Proteins
  • DNA-Binding Proteins
  • Nuclear Proteins
  • RMI1 protein, human
  • RMI2 protein, human
  • RNA, Small Interfering
  • Rif1 protein, human
  • Telomere-Binding Proteins
  • DNA
  • Bloom syndrome protein
  • RecQ Helicases
Topics
  • Amino Acid Sequence
  • Animals
  • Blotting, Western
  • Carrier Proteins (antagonists & inhibitors, genetics, metabolism)
  • Cell Line
  • Chickens
  • DNA (genetics, metabolism)
  • DNA Replication
  • DNA-Binding Proteins (antagonists & inhibitors, genetics, metabolism)
  • HeLa Cells
  • Humans
  • Immunoprecipitation
  • Kidney (cytology, metabolism)
  • Molecular Sequence Data
  • Nuclear Proteins (antagonists & inhibitors, genetics, metabolism)
  • RNA, Small Interfering (pharmacology)
  • RecQ Helicases (antagonists & inhibitors, genetics, metabolism)
  • Sequence Homology, Amino Acid
  • Telomere-Binding Proteins (antagonists & inhibitors, genetics, metabolism)

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