Chromosome breakage is regulated by the interaction of the BLM helicase and topoisomerase IIalpha
Cells deficient in the recQ-like helicase BLM are characterized by chromosome changes that suggest the disruption of normal mechanisms needed to resolve recombination intermediates and to maintain chromosome stability. Human BLM and topoisomerase IIα interact directly via amino acids 489-587 of BLM...
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| Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2011-01, Vol.71 (2), p.561-571 |
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| container_title | Cancer research (Chicago, Ill.) |
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| creator | Russell, Beatriz Bhattacharyya, Saumitri Keirsey, Jeremy Sandy, April Grierson, Patrick Perchiniak, Erin Kavecansky, Juraj Acharya, Samir Groden, Joanna |
| description | Cells deficient in the recQ-like helicase BLM are characterized by chromosome changes that suggest the disruption of normal mechanisms needed to resolve recombination intermediates and to maintain chromosome stability. Human BLM and topoisomerase IIα interact directly via amino acids 489-587 of BLM and colocalize predominantly in late G2 and M phases of the cell cycle. Deletion of this region does not affect the inherent in vitro helicase activity of BLM but inhibits the topoisomerase IIα-dependent enhancement of its activity, based on the analysis of specific DNA substrates that represent some recombination intermediates. Deletion of the interaction domain from BLM fails to correct the elevated chromosome breakage of transfected BLM-deficient cells. Our results demonstrate that the BLM-topoisomerase IIα interaction is important for preventing chromosome breakage and elucidate a DNA repair mechanism that is critical to maintain chromosome stability in cells and to prevent tumor formation. |
| doi_str_mv | 10.1158/0008-5472.CAN-10-1727 |
| format | Article |
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Human BLM and topoisomerase IIα interact directly via amino acids 489-587 of BLM and colocalize predominantly in late G2 and M phases of the cell cycle. Deletion of this region does not affect the inherent in vitro helicase activity of BLM but inhibits the topoisomerase IIα-dependent enhancement of its activity, based on the analysis of specific DNA substrates that represent some recombination intermediates. Deletion of the interaction domain from BLM fails to correct the elevated chromosome breakage of transfected BLM-deficient cells. 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Human BLM and topoisomerase IIα interact directly via amino acids 489-587 of BLM and colocalize predominantly in late G2 and M phases of the cell cycle. Deletion of this region does not affect the inherent in vitro helicase activity of BLM but inhibits the topoisomerase IIα-dependent enhancement of its activity, based on the analysis of specific DNA substrates that represent some recombination intermediates. Deletion of the interaction domain from BLM fails to correct the elevated chromosome breakage of transfected BLM-deficient cells. Our results demonstrate that the BLM-topoisomerase IIα interaction is important for preventing chromosome breakage and elucidate a DNA repair mechanism that is critical to maintain chromosome stability in cells and to prevent tumor formation.</description><subject>Antigens, Neoplasm - genetics</subject><subject>Antigens, Neoplasm - metabolism</subject><subject>Cell Cycle - physiology</subject><subject>Cell Division - physiology</subject><subject>Cell Line, Tumor</subject><subject>Chromosome Breakage</subject><subject>DNA Topoisomerases, Type II - genetics</subject><subject>DNA Topoisomerases, Type II - metabolism</subject><subject>DNA, Neoplasm - metabolism</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>G2 Phase - physiology</subject><subject>HCT116 Cells</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>RecQ Helicases - genetics</subject><subject>RecQ Helicases - metabolism</subject><subject>Transfection</subject><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1kMlOwzAURS0kREvhE0DesXLxEA9ZloihUoFN95ETvzSBJA52suDvSaGsnnTu0ZXuQ-iG0TVj0txTSg2RiebrbPNGGCVMc32GlkwKQ3SSyAW6jPFj1iSj8gItOOM8EYlZIpvVwXc--g5wEcB-2gPgJuIAh6m1IzhcfOOxnlk_QrDl2Pge--oXPexecQ1tU9oI2PYOj37wzbEqHMl2a9uhtlfovLJthOvTXaH90-M-eyG79-dtttmRQUpDmCpVqhlokVaKc-mkAGWEU0JpKY6B5QUkbp6U0IoacGkFzGnFSi2N1WKF7v5qh-C_Johj3jWxhLa1Pfgp5mbey5hK09m8PZlT0YHLh9B0Nnzn_08RP7gAYkc</recordid><startdate>20110115</startdate><enddate>20110115</enddate><creator>Russell, Beatriz</creator><creator>Bhattacharyya, Saumitri</creator><creator>Keirsey, Jeremy</creator><creator>Sandy, April</creator><creator>Grierson, Patrick</creator><creator>Perchiniak, Erin</creator><creator>Kavecansky, Juraj</creator><creator>Acharya, Samir</creator><creator>Groden, Joanna</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20110115</creationdate><title>Chromosome breakage is regulated by the interaction of the BLM helicase and topoisomerase IIalpha</title><author>Russell, Beatriz ; 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| ispartof | Cancer research (Chicago, Ill.), 2011-01, Vol.71 (2), p.561-571 |
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| language | eng |
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| source | MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals |
| subjects | Antigens, Neoplasm - genetics Antigens, Neoplasm - metabolism Cell Cycle - physiology Cell Division - physiology Cell Line, Tumor Chromosome Breakage DNA Topoisomerases, Type II - genetics DNA Topoisomerases, Type II - metabolism DNA, Neoplasm - metabolism DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism G2 Phase - physiology HCT116 Cells HeLa Cells Humans RecQ Helicases - genetics RecQ Helicases - metabolism Transfection |
| title | Chromosome breakage is regulated by the interaction of the BLM helicase and topoisomerase IIalpha |
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