TRF2 binds branched DNA to safeguard telomere integrity Journal Article
| Authors: | Schmutz, I.; Timashev, L.; Xie, W.; Patel, D. J.; de Lange, T. |
| Article Title: | TRF2 binds branched DNA to safeguard telomere integrity |
| Abstract: | Although t-loops protect telomeres, they are at risk of cleavage by Holliday junction (HJ) resolvases if branch migration converts the three-way t-loop junction into four-way HJs. T-loop cleavage is repressed by the TRF2 basic domain, which binds three- and four-way junctions and protects HJs in vitro. By replacing the basic domain with bacterial-protein domains binding three- and four-way junctions, we demonstrated the in vivo relevance of branched-DNA binding. Branched-DNA binding also repressed PARP1, presumably by masking the PARP1 site in the t-loop junction. Although PARP1 recruits HJ resolvases and promotes t-loop cleavage, PARP1 activation alone did not result in t-loop cleavage, thus suggesting that the basic domain also prevents formation of HJs. Concordantly, removal of HJs by BLM helicase mitigated t-loop cleavage in response to loss of the basic domain. We propose that TRF2 masks and stabilizes the t-loop three-way junction, thereby protecting telomeres from detrimental deletions and PARP1 activation. © 2017 Nature America, Inc., part of Springer Nature. All rights reserved. |
| Journal Title: | Nature Structural and Molecular Biology |
| Volume: | 24 |
| Issue: | 9 |
| ISSN: | 1545-9993 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2017-09-01 |
| Start Page: | 734 |
| End Page: | 742 |
| Language: | English |
| DOI: | 10.1038/nsmb.3451 |
| PROVIDER: | scopus |
| PUBMED: | 28805810 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 October 2017 -- Source: Scopus |
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