Structure/Function Analysis of the Saccharomyces cerevisiae Trf4/Pol σ DNA Polymerase

作者: David Fitzhugh , Carrie Adams , Zhenghe Wang , Clemence Vu , Michael F. Christman

DOI: 10.1093/GENETICS/160.2.381

关键词:

摘要: The Trf4p/Pol sigma DNA polymerase (formerly kappa) couples replication to the establishment of sister chromatid cohesion. is encoded by two redundant homologs in Saccharomyces cerevisiae, TRF4 and TRF5, that together define a fourth essential nuclear yeast probably all eukaryotes. Here we present thorough genetic analysis founding member this novel family polymerases, TRF4. Analyses mutants carrying 1 34 "surface-targeted" alanine scanning mutations have identified those regions required for Pol sigma's function, its role double-strand break repair, association with chromosomes. data strongly support importance predicted structural similarity beta superfamily as critical repair functions. Surprisingly, five lethal lie outside homology C-terminal region. protein possesses Mg2+-dependent 3' 5' exonuclease activity. Cell cycle reveals associates chromosomes G1, S, G2 phases, but abolished coincident dissolution cohesion at metaphase-to-anaphase transition.

参考文章(32)
Michelle G. Lihou, Yaw-Huei Hsiang, Leroy F. Liu, Arrest of replication forks by drug-stabilized topoisomerase I-DNA cleavable complexes as a mechanism of cell killing by camptothecin Cancer Research. ,vol. 49, pp. 5077- 5082 ,(1989)
Kohta Takahashi, Mitsuhiro Yanagida, Replication Meets Cohesion Science. ,vol. 289, pp. 735- 736 ,(2000) , 10.1126/SCIENCE.289.5480.735
John R. Pringle, David B. Kaback, H. Yde Steensma, Janet Hirschman, Diane Ruezinsky, Kevin G. Coleman, Paul W. Oeller, Temperature-sensitive lethal mutations on yeast chromosome I appear to define only a small number of genes. Genetics. ,vol. 108, pp. 67- 90 ,(1984) , 10.1093/GENETICS/108.1.67
D G Drubin, K F Wertman, D Botstein, Systematic mutational analysis of the yeast ACT1 gene. Genetics. ,vol. 132, pp. 337- 350 ,(1992) , 10.1093/GENETICS/132.2.337
John L. Nitiss, James C. Wang, Mechanisms of cell killing by drugs that trap covalent complexes between DNA topoisomerases and DNA. Molecular Pharmacology. ,vol. 50, pp. 1095- 1102 ,(1996)
Carrie Walowsky, David J. Fitzhugh, Irene B. Castaño, Justina Y. Ju, Nikki A. Levin, Michael F. Christman, The topoisomerase-related function gene TRF4 affects cellular sensitivity to the antitumor agent camptothecin. Journal of Biological Chemistry. ,vol. 274, pp. 7302- 7308 ,(1999) , 10.1074/JBC.274.11.7302
Jef D. Boeke, Francois La Croute, Gerald R. Fink, A positive selection for mutants lacking orotidine-5'-phosphate decarboxylase activity in yeast: 5-fluoro-orotic acid resistance. Molecular Genetics and Genomics. ,vol. 197, pp. 345- 346 ,(1984) , 10.1007/BF00330984
Aaron F. Straight, Andrew S. Belmont, Carmen C. Robinett, Andrew W. Murray, GFP tagging of budding yeast chromosomes reveals that protein–protein interactions can mediate sister chromatid cohesion Current Biology. ,vol. 6, pp. 1599- 1608 ,(1996) , 10.1016/S0960-9822(02)70783-5
Rafal Ciosk, Masaki Shirayama, Anna Shevchenko, Tomoyuki Tanaka, Attila Toth, Andrej Shevchenko, Kim Nasmyth, Cohesin's Binding to Chromosomes Depends on a Separate Complex Consisting of Scc2 and Scc4 Proteins Molecular Cell. ,vol. 5, pp. 243- 254 ,(2000) , 10.1016/S1097-2765(00)80420-7
W. Xiao, Barbara L. Chow, Lane Rathgeber, The repair of DNA methylation damage in Saccharomyces cerevisiae Current Genetics. ,vol. 30, pp. 461- 468 ,(1996) , 10.1007/S002940050157