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The Transcription Factor TFII-I Promotes DNA Translesion Synthesis and Genomic Stability


DNA translesion synthesis (TLS) allows the DNA replication machinery to replicate past damaged bases, thus increasing cellular tolerance for DNA damage and maintaining genomic stability. Suppression of TLS is expected to enhance the efficacy of the anti-cancer drug, cisplatin. TLS employs a special set of DNA polymerases, including Pol ζ. The TLS polymerases are also involved in somatic hypermutation and proper immune response in mammals. Thus, it is critical to understand the underlying mechanisms of TLS. In this study, we have discovered the transcription factor TFII-I as a new Pol ζ-binding protein in human cells. We show that TFII-I is indeed required for TLS and DNA damage tolerance. We further delineate the mechanism by which TFII-I contributes to TLS. Our study significantly advances the molecular understanding of TLS, and provides a fascinating example of component sharing among disparate nuclear processes. Finally, because one copy of the TFII-I gene is deleted in Williams-Beuren syndrome (WBS), our work implicates TLS deficiency as a potential causal factor of this human genetic disorder.


Vyšlo v časopise: The Transcription Factor TFII-I Promotes DNA Translesion Synthesis and Genomic Stability. PLoS Genet 10(6): e32767. doi:10.1371/journal.pgen.1004419
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004419

Souhrn

DNA translesion synthesis (TLS) allows the DNA replication machinery to replicate past damaged bases, thus increasing cellular tolerance for DNA damage and maintaining genomic stability. Suppression of TLS is expected to enhance the efficacy of the anti-cancer drug, cisplatin. TLS employs a special set of DNA polymerases, including Pol ζ. The TLS polymerases are also involved in somatic hypermutation and proper immune response in mammals. Thus, it is critical to understand the underlying mechanisms of TLS. In this study, we have discovered the transcription factor TFII-I as a new Pol ζ-binding protein in human cells. We show that TFII-I is indeed required for TLS and DNA damage tolerance. We further delineate the mechanism by which TFII-I contributes to TLS. Our study significantly advances the molecular understanding of TLS, and provides a fascinating example of component sharing among disparate nuclear processes. Finally, because one copy of the TFII-I gene is deleted in Williams-Beuren syndrome (WBS), our work implicates TLS deficiency as a potential causal factor of this human genetic disorder.


Zdroje

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