| Structural highlights
4o3m is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , ,
| | Gene: | BLM, RECQ2, RECQL3 (HUMAN) |
| Activity: | DNA helicase, with EC number 3.6.4.12 |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Disease
[BLM_HUMAN] Bloom syndrome. The disease is caused by mutations affecting the gene represented in this entry.
Function
[BLM_HUMAN] Participates in DNA replication and repair. Exhibits a magnesium-dependent ATP-dependent DNA-helicase activity that unwinds single- and double-stranded DNA in a 3'-5' direction. Involved in 5'-end resection of DNA during double-strand break (DSB) repair: unwinds DNA and recruits DNA2 which mediates the cleavage of 5'-ssDNA. Negatively regulates sister chromatid exchange (SCE).[1] [2] [3] [4]
Publication Abstract from PubMed
Bloom's syndrome is an autosomal recessive genome-instability disorder associated with a predisposition to cancer, premature aging and developmental abnormalities. It is caused by mutations that inactivate the DNA helicase activity of the BLM protein or nullify protein expression. The BLM helicase has been implicated in the alternative lengthening of telomeres (ALT) pathway, which is essential for the limitless replication of some cancer cells. This pathway is used by 10-15% of cancers, where inhibitors of BLM are expected to facilitate telomere shortening, leading to apoptosis or senescence. Here, the crystal structure of the human BLM helicase in complex with ADP and a 3'-overhang DNA duplex is reported. In addition to the helicase core, the BLM construct used for crystallization (residues 640-1298) includes the RecQ C-terminal (RQC) and the helicase and ribonuclease D C-terminal (HRDC) domains. Analysis of the structure provides detailed information on the interactions of the protein with DNA and helps to explain the mechanism coupling ATP hydrolysis and DNA unwinding. In addition, mapping of the missense mutations onto the structure provides insights into the molecular basis of Bloom's syndrome.
Structure of human Bloom's syndrome helicase in complex with ADP and duplex DNA.,Swan MK, Legris V, Tanner A, Reaper PM, Vial S, Bordas R, Pollard JR, Charlton PA, Golec JM, Bertrand JA Acta Crystallogr D Biol Crystallogr. 2014 May;70(Pt 5):1465-75. doi:, 10.1107/S139900471400501X. Epub 2014 Apr 30. PMID:24816114[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Karow JK, Chakraverty RK, Hickson ID. The Bloom's syndrome gene product is a 3'-5' DNA helicase. J Biol Chem. 1997 Dec 5;272(49):30611-4. PMID:9388193
- ↑ Langland G, Elliott J, Li Y, Creaney J, Dixon K, Groden J. The BLM helicase is necessary for normal DNA double-strand break repair. Cancer Res. 2002 May 15;62(10):2766-70. PMID:12019152
- ↑ Nimonkar AV, Genschel J, Kinoshita E, Polaczek P, Campbell JL, Wyman C, Modrich P, Kowalczykowski SC. BLM-DNA2-RPA-MRN and EXO1-BLM-RPA-MRN constitute two DNA end resection machineries for human DNA break repair. Genes Dev. 2011 Feb 15;25(4):350-62. doi: 10.1101/gad.2003811. PMID:21325134 doi:http://dx.doi.org/10.1101/gad.2003811
- ↑ Wan L, Han J, Liu T, Dong S, Xie F, Chen H, Huang J. Scaffolding protein SPIDR/KIAA0146 connects the Bloom syndrome helicase with homologous recombination repair. Proc Natl Acad Sci U S A. 2013 Jun 25;110(26):10646-51. doi:, 10.1073/pnas.1220921110. Epub 2013 Mar 18. PMID:23509288 doi:http://dx.doi.org/10.1073/pnas.1220921110
- ↑ Swan MK, Legris V, Tanner A, Reaper PM, Vial S, Bordas R, Pollard JR, Charlton PA, Golec JM, Bertrand JA. Structure of human Bloom's syndrome helicase in complex with ADP and duplex DNA. Acta Crystallogr D Biol Crystallogr. 2014 May;70(Pt 5):1465-75. doi:, 10.1107/S139900471400501X. Epub 2014 Apr 30. PMID:24816114 doi:http://dx.doi.org/10.1107/S139900471400501X
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