Yeast Transcription Termination Factor Rtt103 Functions in DNA Damage Response

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2012 Feb 23

PMID 22355353

Citations 12

Authors

Indukuri Srividya

Sirupangi Tirupataiah

Krishnaveni Mishra

Affiliations

Soon will be listed here.

Abstract

YKu70/YKu80 is a heterodimer that is essential for repair of DNA double strand breaks through non-homologous end joining pathway in the yeast Saccharomyces cerevisiae. Yku70/80 proteins are associated with telomeres and are important for maintaining the integrity of telomeres. These proteins protect telomeres from recombination events, nuclease attacks, support the formation of heterochromatin at telomeres and anchor telomeres to the nuclear periphery. To identify components in molecular networks involved in the multiple functions of Yku70/80 complex, we performed a genetic screen for suppressors of yku70 deletion. One of the suppressors identified was RTT103, which encodes a protein implicated in transcription termination. We show that rtt103Δ are sensitive to multiple forms of genome insults and that RTT103 is essential for recovery from DNA double strand breaks in the chromosome. We further show that Rtt103 associates with sites of DNA breaks and hence is likely to play a direct role in response to DNA damage.

Citing Articles

Hydroxyurea and inactivation of checkpoint kinase MEC1 inhibit transcription termination and pre-mRNA cleavage at polyadenylation sites in budding yeast.

Kaur P, Nagar S, Mehta R, Sahadeo K, Vancura A Sci Rep. 2023; 13(1):13106.

PMID: 37567961 PMC: 10421882. DOI: 10.1038/s41598-023-40294-3.

Transcription termination complex, Rtt103-Rai1-Rat1, regulates sub-telomeric transcripts in .

Ramalingam K, Mishra K RNA Biol. 2023; 20(1):95-108.

PMID: 36974034 PMC: 10054321. DOI: 10.1080/15476286.2023.2192552.

RNA-Mediated Regulation of Meiosis in Budding Yeast.

Pondugala V, Mishra K Noncoding RNA. 2022; 8(6).

PMID: 36412912 PMC: 9680404. DOI: 10.3390/ncrna8060077.

Suppression of telomere capping defects of Saccharomyces cerevisiae yku70 and yku80 mutants by telomerase.

Holland C, Sanderson B, Titus J, Weis M, Riojas A, Malczewskyj E G3 (Bethesda). 2021; 11(12).

PMID: 34718547 PMC: 8664480. DOI: 10.1093/g3journal/jkab359.

Genome stability is guarded by yeast Rtt105 through multiple mechanisms.

Corda Y, Maestroni L, Luciano P, Najem M, Geli V Genetics. 2021; 217(2).

PMID: 33724421 PMC: 8045678. DOI: 10.1093/genetics/iyaa035.

References

Lunde B, Reichow S, Kim M, Suh H, Leeper T, Yang F . Cooperative interaction of transcription termination factors with the RNA polymerase II C-terminal domain. Nat Struct Mol Biol. 2010; 17(10):1195-201. PMC: 2950884. DOI: 10.1038/nsmb.1893. View

Xu F, Zhang K, Grunstein M . Acetylation in histone H3 globular domain regulates gene expression in yeast. Cell. 2005; 121(3):375-85. DOI: 10.1016/j.cell.2005.03.011. View

Hanway D, Chin J, Xia G, Oshiro G, Winzeler E, Romesberg F . Previously uncharacterized genes in the UV- and MMS-induced DNA damage response in yeast. Proc Natl Acad Sci U S A. 2002; 99(16):10605-10. PMC: 124988. DOI: 10.1073/pnas.152264899. View

Milne G, Jin S, Shannon K, Weaver D . Mutations in two Ku homologs define a DNA end-joining repair pathway in Saccharomyces cerevisiae. Mol Cell Biol. 1996; 16(8):4189-98. PMC: 231416. DOI: 10.1128/MCB.16.8.4189. View

Paulsen R, Soni D, Wollman R, Hahn A, Yee M, Guan A . A genome-wide siRNA screen reveals diverse cellular processes and pathways that mediate genome stability. Mol Cell. 2009; 35(2):228-39. PMC: 2772893. DOI: 10.1016/j.molcel.2009.06.021. View

Vodenicharov M, Laterreur N, Wellinger R . Telomere capping in non-dividing yeast cells requires Yku and Rap1. EMBO J. 2010; 29(17):3007-19. PMC: 2944054. DOI: 10.1038/emboj.2010.155. View

Feldmann H, Driller L, Meier B, Mages G, KELLERMANN J, Winnacker E . HDF2, the second subunit of the Ku homologue from Saccharomyces cerevisiae. J Biol Chem. 1996; 271(44):27765-9. DOI: 10.1074/jbc.271.44.27765. View

Gasch A, Huang M, Metzner S, Botstein D, Elledge S, Brown P . Genomic expression responses to DNA-damaging agents and the regulatory role of the yeast ATR homolog Mec1p. Mol Biol Cell. 2001; 12(10):2987-3003. PMC: 60150. DOI: 10.1091/mbc.12.10.2987. View

Aguilera A . The connection between transcription and genomic instability. EMBO J. 2002; 21(3):195-201. PMC: 125829. DOI: 10.1093/emboj/21.3.195. View

10.

Marcand S, Pardo B, Gratias A, Cahun S, Callebaut I . Multiple pathways inhibit NHEJ at telomeres. Genes Dev. 2008; 22(9):1153-8. PMC: 2335312. DOI: 10.1101/gad.455108. View

11.

Harrison J, Haber J . Surviving the breakup: the DNA damage checkpoint. Annu Rev Genet. 2006; 40:209-35. DOI: 10.1146/annurev.genet.40.051206.105231. View

12.

Mirkin N, Fonseca D, Mohammed S, Cevher M, Manley J, Kleiman F . The 3' processing factor CstF functions in the DNA repair response. Nucleic Acids Res. 2008; 36(6):1792-804. PMC: 2330234. DOI: 10.1093/nar/gkn005. View

13.

Cherry J, Adler C, Ball C, Chervitz S, Dwight S, Hester E . SGD: Saccharomyces Genome Database. Nucleic Acids Res. 1998; 26(1):73-9. PMC: 147204. DOI: 10.1093/nar/26.1.73. View

14.

Pellicioli A, Lucca C, Liberi G, Marini F, Lopes M, Plevani P . Activation of Rad53 kinase in response to DNA damage and its effect in modulating phosphorylation of the lagging strand DNA polymerase. EMBO J. 1999; 18(22):6561-72. PMC: 1171719. DOI: 10.1093/emboj/18.22.6561. View

15.

Fisher T, Taggart A, Zakian V . Cell cycle-dependent regulation of yeast telomerase by Ku. Nat Struct Mol Biol. 2004; 11(12):1198-205. DOI: 10.1038/nsmb854. View

16.

Longtine M, McKenzie 3rd A, DeMarini D, Shah N, Wach A, Brachat A . Additional modules for versatile and economical PCR-based gene deletion and modification in Saccharomyces cerevisiae. Yeast. 1998; 14(10):953-61. DOI: 10.1002/(SICI)1097-0061(199807)14:10<953::AID-YEA293>3.0.CO;2-U. View

17.

Jelinsky S, Estep P, Church G, Samson L . Regulatory networks revealed by transcriptional profiling of damaged Saccharomyces cerevisiae cells: Rpn4 links base excision repair with proteasomes. Mol Cell Biol. 2000; 20(21):8157-67. PMC: 86425. DOI: 10.1128/MCB.20.21.8157-8167.2000. View

18.

Skourti-Stathaki K, Proudfoot N, Gromak N . Human senataxin resolves RNA/DNA hybrids formed at transcriptional pause sites to promote Xrn2-dependent termination. Mol Cell. 2011; 42(6):794-805. PMC: 3145960. DOI: 10.1016/j.molcel.2011.04.026. View

19.

Enyenihi A, Saunders W . Large-scale functional genomic analysis of sporulation and meiosis in Saccharomyces cerevisiae. Genetics. 2003; 163(1):47-54. PMC: 1462418. DOI: 10.1093/genetics/163.1.47. View

20.

Wood R, Mitchell M, Lindahl T . Human DNA repair genes, 2005. Mutat Res. 2005; 577(1-2):275-83. DOI: 10.1016/j.mrfmmm.2005.03.007. View