TY - JOUR
T1 - BLM is an early responder to DNA double-strand breaks
AU - Karmakar, Parimal
AU - Seki, Masayuki
AU - Kanamori, Makoto
AU - Hashiguchi, Kazunari
AU - Ohtsuki, Makoto
AU - Murata, Eriko
AU - Inoue, Eri
AU - Tada, Shusuke
AU - Lan, Li
AU - Yasui, Akira
AU - Enomoto, Takemi
N1 - Funding Information:
We thank Dr. S. Takeda for kindly providing DNA-PKcs −/−/− ,XRCC3 −/− ,RAD52 −/− , and RAD54 −/− cells, Dr. K. Yamamoto and Dr. M. Kobayashi for ATM −/− and RAD17 −/− cells, Dr. K. Komatsu and Dr. H. Tauchi for NBS1 −/−/− cells, and Dr. Y Furuichi and Dr. T. Matsumoto for WRN −/− cells. P. Karmakar was supported by JSPS Invitation Fellowship Programs for Research in Japan. This work was supported by Grants-in-Aid for Scientific Research and for Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
PY - 2006/9/15
Y1 - 2006/9/15
N2 - 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 10 s and colocalizes with γH2AX 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.
AB - 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 10 s and colocalizes with γH2AX 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.
KW - BLM protein
KW - DNA double-strand break repair
KW - DT40 cells
KW - HRDC domain
KW - Laser micro-irradiation
KW - RecQ helicase
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U2 - 10.1016/j.bbrc.2006.07.037
DO - 10.1016/j.bbrc.2006.07.037
M3 - Article
C2 - 16876111
AN - SCOPUS:33746778751
SN - 0006-291X
VL - 348
SP - 62
EP - 69
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -
