FANCJ promotes DNA synthesis through G-quadruplex structures
View/ Open
Author
Castillo Bosch, Pau
Segura-Bayona, Sandra
Koole, Wouter
van Heteren, Jane T
Tijsterman, Marcel
Knipscheer, Puck
Published Version
https://doi.org/10.15252/embj.201488663Metadata
Show full item recordCitation
Castillo Bosch, Pau, Sandra Segura-Bayona, Wouter Koole, Jane T van Heteren, James M Dewar, Marcel Tijsterman, and Puck Knipscheer. 2014. “FANCJ promotes DNA synthesis through G-quadruplex structures.” The EMBO Journal 33 (21): 2521-2533. doi:10.15252/embj.201488663. http://dx.doi.org/10.15252/embj.201488663.Abstract
Our genome contains many G-rich sequences, which have the propensity to fold into stable secondary DNA structures called G4 or G-quadruplex structures. These structures have been implicated in cellular processes such as gene regulation and telomere maintenance. However, G4 sequences are prone to mutations particularly upon replication stress or in the absence of specific helicases. To investigate how G-quadruplex structures are resolved during DNA replication, we developed a model system using ssDNA templates and Xenopus egg extracts that recapitulates eukaryotic G4 replication. Here, we show that G-quadruplex structures form a barrier for DNA replication. Nascent strand synthesis is blocked at one or two nucleotides from the G4. After transient stalling, G-quadruplexes are efficiently unwound and replicated. In contrast, depletion of the FANCJ/BRIP1 helicase causes persistent replication stalling at G-quadruplex structures, demonstrating a vital role for this helicase in resolving these structures. FANCJ performs this function independently of the classical Fanconi anemia pathway. These data provide evidence that the G4 sequence instability in FANCJ−/− cells and Fancj/dog1 deficient C. elegans is caused by replication stalling at G-quadruplexes.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4282361/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:13890806
Collections
- HMS Scholarly Articles [17922]
Contact administrator regarding this item (to report mistakes or request changes)