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Role of PCNA and TLS polymerases in D-loop extension during homologous recombination in humans
M. Sebesta, P. Burkovics, S. Juhasz, S. Zhang, JE. Szabo, MY. Lee, L. Haracska, L. Krejci,
Jazyk angličtina Země Nizozemsko
Typ dokumentu časopisecké články, práce podpořená grantem
- MeSH
- DNA-dependentní DNA-polymerasy chemie fyziologie MeSH
- DNA-polymerasa III chemie fyziologie MeSH
- HeLa buňky MeSH
- homologní rekombinace * MeSH
- jednovláknová DNA biosyntéza MeSH
- lidé MeSH
- osmolární koncentrace MeSH
- poškození DNA MeSH
- proliferační antigen buněčného jádra chemie fyziologie MeSH
- protein FUS vázající RNA chemie fyziologie MeSH
- rekombinasa Rad51 chemie MeSH
- replikace DNA MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Homologous recombination (HR) is essential for maintaining genomic integrity, which is challenged by a wide variety of potentially lethal DNA lesions. Regardless of the damage type, recombination is known to proceed by RAD51-mediated D-loop formation, followed by DNA repair synthesis. Nevertheless, the participating polymerases and extension mechanism are not well characterized. Here, we present a reconstitution of this step using purified human proteins. In addition to Pol δ, TLS polymerases, including Pol η and Pol κ, also can extend D-loops. In vivo characterization reveals that Pol η and Pol κ are involved in redundant pathways for HR. In addition, the presence of PCNA on the D-loop regulates the length of the extension tracks by recruiting various polymerases and might present a regulatory point for the various recombination outcomes.
Citace poskytuje Crossref.org
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- $a Homologous recombination (HR) is essential for maintaining genomic integrity, which is challenged by a wide variety of potentially lethal DNA lesions. Regardless of the damage type, recombination is known to proceed by RAD51-mediated D-loop formation, followed by DNA repair synthesis. Nevertheless, the participating polymerases and extension mechanism are not well characterized. Here, we present a reconstitution of this step using purified human proteins. In addition to Pol δ, TLS polymerases, including Pol η and Pol κ, also can extend D-loops. In vivo characterization reveals that Pol η and Pol κ are involved in redundant pathways for HR. In addition, the presence of PCNA on the D-loop regulates the length of the extension tracks by recruiting various polymerases and might present a regulatory point for the various recombination outcomes.
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