Dna2 nuclease-helicase structure, mechanism and regulation by Rpa Journal Article
| Authors: | Zhou, C.; Pourmal, S.; Pavletich, N. P. |
| Article Title: | Dna2 nuclease-helicase structure, mechanism and regulation by Rpa |
| Abstract: | The Dna2 nuclease-helicase maintains genomic integrity by processing DNA double-strand breaks, Okazaki fragments and stalled replication forks. Dna2 requires ssDNA ends, and is dependent on the ssDNA-binding protein Rpa, which controls cleavage polarity. Here we present the 2.3 Å structure of intact mouse Dna2 bound to a 15-nucleotide ssDNA. The nuclease active site is embedded in a long, narrow tunnel through which the DNA has to thread. The helicase domain is required for DNA binding but not threading. We also present the structure of a flexibly-tethered Dna2-Rpa interaction that recruits Dna2 to Rpa-coated DNA. We establish that a second Dna2-Rpa interaction is mutually exclusive with Rpa-DNA interactions and mediates the displacement of Rpa from ssDNA. This interaction occurs at the nuclease tunnel entrance and the 5’ end of the Rpa-DNA complex. Hence, it only displaces Rpa from the 5’ but not 3’ end, explaining how Rpa regulates cleavage polarity. © Zhou et al. |
| Journal Title: | eLife |
| Volume: | 4 |
| ISSN: | 2050-084X |
| Publisher: | eLife Sciences Publications Ltd. |
| Date Published: | 2015-10-22 |
| Start Page: | e09832 |
| Language: | English |
| DOI: | 10.7554/eLife.09832 |
| PROVIDER: | scopus |
| PMCID: | PMC4716839 |
| PUBMED: | 26491943 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 February 2016 -- Source: Scopus |
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