BLM is an early responder to DNA double-strand breaks.

Abstract	Bloom syndrome (BS) is an autosomal recessive disorder characterized by a marked predisposition to cancer and elevated genomic instability. The defective protein in BS, BLM, is a member of the RecQ helicase family and is believed to function in various DNA transactions, including in replication, repair, and recombination. Here, we show that both endogenous and overexpressed human BLM accumulates at sites of laser light-induced DNA double-strand breaks within 10s and colocalizes with gammaH2AX and ATM. Like its RecQ helicase family member, WRN, the defective protein in Werner syndrome, dissection of the BLM protein revealed that its HRDC domain is sufficient for its recruitment to the damaged sites. In addition, we confirmed that the C-terminal region spanning amino acids 1250-1292 within the HRDC domain is necessary for BLM recruitment. To identify additional proteins required for the recruitment of BLM, we examined the recruitment of BLM in various mutants generated from chicken DT40 cells and found that the early accumulation of BLM was not dependent on the presence of ATM, RAD17, DNA-PKcs, NBS1, XRCC3, RAD52, RAD54, or WRN. Thus, HRDC domain in DNA helicases is a common early responder to DNA double-strand breaks, enabling BLM and WRN to be involved in DNA repair.
Authors	Parimal Karmakar, Masayuki Seki, Makoto Kanamori, Kazunari Hashiguchi, Makoto Ohtsuki, Eriko Murata, Eri Inoue, Shusuke Tada, Li Lan, Akira Yasui, Takemi Enomoto
Journal	Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 348 Issue 1 Pg. 62-9 (Sep 15 2006) ISSN: 0006-291X [Print] United States
PMID	16876111 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Cell Cycle Proteins DNA-Binding Proteins H2AX protein, human Histones Tumor Suppressor Proteins Green Fluorescent Proteins DNA ATM protein, human Ataxia Telangiectasia Mutated Proteins Protein Serine-Threonine Kinases Adenosine Triphosphatases Bloom syndrome protein RECQL protein, human DNA Helicases RecQ Helicases
Topics	Adenosine Triphosphatases (genetics) Amino Acid Motifs Ataxia Telangiectasia Mutated Proteins Binding Sites Bloom Syndrome (genetics) Cell Cycle Proteins (genetics) Cell Line DNA (genetics) DNA Damage DNA Helicases (genetics) DNA Repair DNA-Binding Proteins (genetics) Green Fluorescent Proteins Histones (genetics) Humans Lasers Protein Binding Protein Serine-Threonine Kinases (genetics) Protein Structure, Tertiary RecQ Helicases Tumor Suppressor Proteins (genetics)

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