title: 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.affiliation: Molecular Cell Biology Laboratory, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan. pkarmakar_28@yahoo.co.in
authors.forename: Parimal
authors.initials: P
authors.lastname: Karmakar
authors.forename: Masayuki
authors.initials: M
authors.lastname: Seki
authors.forename: Makoto
authors.initials: M
authors.lastname: Kanamori
authors.forename: Kazunari
authors.initials: K
authors.lastname: Hashiguchi
authors.forename: Makoto
authors.initials: M
authors.lastname: Ohtsuki
authors.forename: Eriko
authors.initials: E
authors.lastname: Murata
authors.forename: Eri
authors.initials: E
authors.lastname: Inoue
authors.forename: Shusuke
authors.initials: S
authors.lastname: Tada
authors.forename: Li
authors.initials: L
authors.lastname: Lan
authors.forename: Akira
authors.initials: A
authors.lastname: Yasui
authors.forename: Takemi
authors.initials: T
authors.lastname: Enomoto
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D020816:Amino Acid Motifs; D064007:Ataxia Telangiectasia Mutated Proteins; D001665:Binding Sites; D001816:Bloom Syndrome / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D002460:Cell Line; D004247:DNA / Q000235:genetics; D004249:DNA Damage; D004265:DNA Helicases / Q000235:genetics*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics; D049452:Green Fluorescent Proteins; D006657:Histones / Q000235:genetics; D006801:Humans; D007834:Lasers; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D017434:Protein Structure, Tertiary; D053484:RecQ Helicases; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C468783:H2AX protein, human; D006657:Histones; D025521:Tumor Suppressor Proteins; D049452:Green Fluorescent Proteins; D004247:DNA; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D000251:Adenosine Triphosphatases; C097151:Bloom syndrome protein; C506725:RECQL protein, human; D004265:DNA Helicases; D053484:RecQ Helicases