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PLoS Genet. 2014 Jun 12;10(6):e1004419. doi: 10.1371/journal.pgen.1004419. eCollection 2014.

The transcription factor TFII-I promotes DNA translesion synthesis and genomic stability.

Author information

1
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America; Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
2
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America; Howard Hughes Medical Institute, Chevy Chase, Maryland, United States of America.
3
Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
4
Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, New York, United States of America.

Abstract

Translesion synthesis (TLS) enables DNA replication through damaged bases, increases cellular DNA damage tolerance, and maintains genomic stability. The sliding clamp PCNA and the adaptor polymerase Rev1 coordinate polymerase switching during TLS. The polymerases Pol η, ι, and κ insert nucleotides opposite damaged bases. Pol ζ, consisting of the catalytic subunit Rev3 and the regulatory subunit Rev7, then extends DNA synthesis past the lesion. Here, we show that Rev7 binds to the transcription factor TFII-I in human cells. TFII-I is required for TLS and DNA damage tolerance. The TLS function of TFII-I appears to be independent of its role in transcription, but requires homodimerization and binding to PCNA. We propose that TFII-I bridges PCNA and Pol ζ to promote TLS. Our findings extend the general principle of component sharing among divergent nuclear processes and implicate TLS deficiency as a possible contributing factor in Williams-Beuren syndrome.

PMID:
24922507
PMCID:
PMC4055408
DOI:
10.1371/journal.pgen.1004419
[Indexed for MEDLINE]
Free PMC Article
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