This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhang, R. Articles by Harris, C. C. Search for Related Content PubMed PubMed Citation Articles by Zhang, R. Articles by Harris, C. C.

BLM Helicase Facilitates Mus81 Endonuclease Activity in Human Cells

¹ Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland; and ² Department of Molecular Biology and Department of Cell Biology, The Scripps Research Institute, La Jolla, California

Requests for reprints: Curtis C. Harris, Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Room 3068, Building 37, 37 Convent Drive, Bethesda, MD 20892-4255. Phone: 301-496-2048; Fax: 301-496-0497; E-mail: curtis_harris{at}nih.gov.

Bloom syndrome is a rare, autosomal recessive inherited disorder in humans. The product of the Bloom syndrome mutated gene, designated BLM, is a member of the RecQ helicase family. BLM has been proposed to function at the interface of replication and recombination, and to facilitate the repair of DNA damage. Here, we report in vivo physical interaction and colocalization of BLM and a DNA structure–specific endonuclease, Mus81, at sites of stalled replication forks outside the promyelocytic leukemia nuclear bodies during the S-phase arrest of the cell cycle. Amino acids 125 to 244 of Mus81 interact with the C-terminal region (amino acids 1,007-1,417) of BLM. Whereas Mus81 does not have any effect on the helicase activity of BLM, BLM can stimulate Mus81 endonuclease activity on the nicked Holliday junctions and 3' flap. This stimulation is due to enhanced binding of Mus81 to the DNA substrates. These data suggest a new function of BLM in cooperating with Mus81 during processing and restoration of stalled replication forks.

Key Words: Endonuclease • helicase • p53 • Rad51 • replication arrest

This article has been cited by other articles:

				P. Matulova, V. Marini, R. C. Burgess, A. Sisakova, Y. Kwon, R. Rothstein, P. Sung, and L. Krejci Cooperativity of Mus81{middle dot}Mms4 with Rad54 in the Resolution of Recombination and Replication Intermediates J. Biol. Chem., March 20, 2009; 284(12): 7733 - 7745. [Abstract] [Full Text] [PDF]

				O. M. Mazina and A. V. Mazin Human Rad54 protein stimulates human Mus81-Eme1 endonuclease PNAS, November 25, 2008; 105(47): 18249 - 18254. [Abstract] [Full Text] [PDF]

				B. Froget, J. Blaisonneau, S. Lambert, and G. Baldacci Cleavage of Stalled Forks by Fission Yeast Mus81/Eme1 in Absence of DNA Replication Checkpoint Mol. Biol. Cell, February 1, 2008; 19(2): 445 - 456. [Abstract] [Full Text] [PDF]

				J. Grillari, H. Katinger, and R. Voglauer Contributions of DNA interstrand cross-links to aging of cells and organisms Nucleic Acids Res., December 14, 2007; (2007) gkm1065v1. [Abstract] [Full Text] [PDF]

				J. C. Hope, L. D. Cruzata, A. Duvshani, J. Mitsumoto, M. Maftahi, and G. A. Freyer Mus81-Eme1-Dependent and -Independent Crossovers Form in Mitotic Cells during Double-Strand Break Repair in Schizosaccharomyces pombe Mol. Cell. Biol., May 15, 2007; 27(10): 3828 - 3838. [Abstract] [Full Text] [PDF]

				N. Mimida, H. Kitamoto, K. Osakabe, M. Nakashima, Y. Ito, W.-D. Heyer, S. Toki, and H. Ichikawa Two Alternatively Spliced Transcripts Generated from OsMUS81, a Rice Homolog of Yeast MUS81, Are Up-Regulated by DNA-Damaging Treatments Plant Cell Physiol., April 1, 2007; 48(4): 648 - 654. [Abstract] [Full Text] [PDF]