title: The transcription factor TFII-I promotes DNA translesion synthesis and genomic stability.
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.
authors.affiliation: 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.
authors.forename: Farjana J
authors.initials: FJ
authors.lastname: Fattah
authors.affiliation: 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.
authors.forename: Kodai
authors.initials: K
authors.lastname: Hara
authors.affiliation: Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
authors.forename: Kazi R
authors.initials: KR
authors.lastname: Fattah
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, New York, United States of America.
authors.forename: Chenyi
authors.initials: C
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Nan
authors.initials: N
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Ross
authors.initials: R
authors.lastname: Warrington
authors.affiliation: Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
authors.forename: David J
authors.initials: DJ
authors.lastname: Chen
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, New York, United States of America.
authors.forename: Pengbo
authors.initials: P
authors.lastname: Zhou
authors.affiliation: 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.
authors.forename: David A
authors.initials: DA
authors.lastname: Boothman
authors.affiliation: 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.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Yu
mesh_terms: D045744:Cell Line, Tumor; D004249:DNA Damage / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D004259:DNA-Directed DNA Polymerase / Q000096:biosynthesis; D042822:Genomic Instability; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D064246:Mad2 Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000096:biosynthesis; D009713:Nucleotidyltransferases / Q000096:biosynthesis; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis / Q000378:metabolism; D019473:Transcription Factors, TFII / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D000099270:Y-Family DNA Polymerases
chemical_list: D004268:DNA-Binding Proteins; D004259:DNA-Directed DNA Polymerase; D064246:Mad2 Proteins; D009687:Nuclear Proteins; D009713:Nucleotidyltransferases; D018809:Proliferating Cell Nuclear Antigen; D019473:Transcription Factors, TFII; C104259:GTF2I protein, human; C120552:MAD2L2 protein, human; C429004:REV1 protein, human; D000099270:Y-Family DNA Polymerases; C118285:REV3L protein, human