Structural mechanisms of human RecQ helicases WRN and BLM
The RecQ family DNA helicases WRN (Werner syndrome protein) and BLM (Bloom syndrome protein) play a key role in protecting the genome against deleterious changes. In humans, mutations in these proteins lead to rare genetic diseases associated with cancer predisposition and accelerated aging. WRN and...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2014-10-01
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| Series: | Frontiers in Genetics |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fgene.2014.00366/full |
| _version_ | 1818980544588808192 |
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| author | Ken eKitano |
| author_facet | Ken eKitano |
| author_sort | Ken eKitano |
| collection | DOAJ |
| description | The RecQ family DNA helicases WRN (Werner syndrome protein) and BLM (Bloom syndrome protein) play a key role in protecting the genome against deleterious changes. In humans, mutations in these proteins lead to rare genetic diseases associated with cancer predisposition and accelerated aging. WRN and BLM are distinguished from other helicases by possessing signature tandem domains toward the C terminus, referred to as the RecQ C-terminal (RQC) and helicase-and-ribonuclease D-C-terminal (HRDC) domains. Although the precise function of the HRDC domain remains unclear, the previous crystal structure of a WRN RQC-DNA complex visualized a central role for the RQC domain in recognizing, binding and unwinding DNA at branch points. In particular, a prominent hairpin structure (the β-wing) within the RQC winged-helix motif acts as a scalpel to induce the unpairing of a Watson-Crick base pair at the DNA duplex terminus. A similar RQC-DNA interaction was also observed in the recent crystal structure of a BLM-DNA complex. I review the latest structures of WRN and BLM, and then provide a docking simulation of BLM with a Holliday junction. The model offers an explanation for the efficient branch migration activity of the RecQ family toward recombination and repair intermediates. |
| first_indexed | 2024-12-20T17:17:07Z |
| format | Article |
| id | doaj.art-387e18153c4f4ce7afcb9360b5201d5a |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-20T17:17:07Z |
| publishDate | 2014-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-387e18153c4f4ce7afcb9360b5201d5a2022-12-21T19:31:58ZengFrontiers Media S.A.Frontiers in Genetics1664-80212014-10-01510.3389/fgene.2014.00366116222Structural mechanisms of human RecQ helicases WRN and BLMKen eKitano0Nara Institute of Science and TechnologyThe RecQ family DNA helicases WRN (Werner syndrome protein) and BLM (Bloom syndrome protein) play a key role in protecting the genome against deleterious changes. In humans, mutations in these proteins lead to rare genetic diseases associated with cancer predisposition and accelerated aging. WRN and BLM are distinguished from other helicases by possessing signature tandem domains toward the C terminus, referred to as the RecQ C-terminal (RQC) and helicase-and-ribonuclease D-C-terminal (HRDC) domains. Although the precise function of the HRDC domain remains unclear, the previous crystal structure of a WRN RQC-DNA complex visualized a central role for the RQC domain in recognizing, binding and unwinding DNA at branch points. In particular, a prominent hairpin structure (the β-wing) within the RQC winged-helix motif acts as a scalpel to induce the unpairing of a Watson-Crick base pair at the DNA duplex terminus. A similar RQC-DNA interaction was also observed in the recent crystal structure of a BLM-DNA complex. I review the latest structures of WRN and BLM, and then provide a docking simulation of BLM with a Holliday junction. The model offers an explanation for the efficient branch migration activity of the RecQ family toward recombination and repair intermediates.http://journal.frontiersin.org/Journal/10.3389/fgene.2014.00366/fullBloom SyndromeWerner SyndromeStructural BiologyDNA helicaseWRNBLM |
| spellingShingle | Ken eKitano Structural mechanisms of human RecQ helicases WRN and BLM Frontiers in Genetics Bloom Syndrome Werner Syndrome Structural Biology DNA helicase WRN BLM |
| title | Structural mechanisms of human RecQ helicases WRN and BLM |
| title_full | Structural mechanisms of human RecQ helicases WRN and BLM |
| title_fullStr | Structural mechanisms of human RecQ helicases WRN and BLM |
| title_full_unstemmed | Structural mechanisms of human RecQ helicases WRN and BLM |
| title_short | Structural mechanisms of human RecQ helicases WRN and BLM |
| title_sort | structural mechanisms of human recq helicases wrn and blm |
| topic | Bloom Syndrome Werner Syndrome Structural Biology DNA helicase WRN BLM |
| url | http://journal.frontiersin.org/Journal/10.3389/fgene.2014.00366/full |
| work_keys_str_mv | AT kenekitano structuralmechanismsofhumanrecqhelicaseswrnandblm |