Fattah Farjana J, Hara Kodai, Fattah Kazi R, Yang Chenyi, Wu Nan, Warrington Ross, Chen David J, Zhou Pengbo, Boothman David A, Yu Hongtao
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.
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.
PLoS Genet. 2014 Jun 12;10(6):e1004419. doi: 10.1371/journal.pgen.1004419. eCollection 2014 Jun.
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.
跨损伤合成（TLS）可使DNA通过受损碱基进行复制，增强细胞对DNA损伤的耐受性，并维持基因组稳定性。滑动夹增殖细胞核抗原（PCNA）和衔接子聚合酶Rev1在TLS过程中协调聚合酶转换。聚合酶Pol η、ι和κ在受损碱基对面插入核苷酸。然后，由催化亚基Rev3和调节亚基Rev7组成的Pol ζ将DNA合成延伸至损伤部位之外。在此，我们表明Rev7在人类细胞中与转录因子TFII-I结合。TFII-I是TLS和DNA损伤耐受性所必需的。TFII-I的TLS功能似乎与其在转录中的作用无关，但需要同型二聚化并与PCNA结合。我们提出TFII-I在PCNA和Pol ζ之间起桥梁作用以促进TLS。我们的发现扩展了不同核过程中成分共享的一般原则，并暗示TLS缺陷可能是威廉姆斯-博伦综合征的一个促成因素。
