The ATM-related Tel1 Protein of Saccharomyces Cerevisiae Controls a Checkpoint Response Following Phleomycin Treatment

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2003 Mar 11

PMID 12626713

Citations 32

Authors

Daisuke Nakada

Toshiyasu Shimomura

Kunihiro Matsumoto

Katsunori Sugimoto

Affiliations

Soon will be listed here.

Abstract

MEC1 and TEL1 encode ATR- and ATM-related proteins in the budding yeast Saccharomyces cerevisiae, respectively. Phleomycin is an agent that catalyzes double-strand breaks in DNA. We show here that both Mec1 and Tel1 regulate the checkpoint response following phleomycin treatment. MEC1 is required for Rad53 phosphorylation and cell-cycle progression delay following phleomycin treatment in G1, S or G2/M phases. The tel1Delta mutation confers a defect in the checkpoint responses to phleomycin treatment in S phase. In addition, the tel1Delta mutation enhances the mec1 defect in activation of the phleomycin-induced checkpoint pathway in S phase. In contrast, the tel1Delta mutation confers only a minor defect in the checkpoint responses in G1 phase and no apparent defect in G2/M phase. Methyl methanesulfonate (MMS) treatment also activates checkpoints, inducing Rad53 phosphorylation in S phase. MMS-induced Rad53 phosphorylation is not detected in mec1Delta mutants during S phase, but occurs in tel1Delta mutants similar to wild-type cells. Finally, Xrs2 is phosphorylated after phleomycin treatment in a TEL1-dependent manner during S phase, whereas no significant Xrs2 phosphorylation is detected after MMS treatment. Together, our results support a model in which Tel1 contributes to checkpoint control in response to phleomycin-induced DNA damage in S phase.

Citing Articles

Regulation of Pkc1 Hyper-Phosphorylation by Genotoxic Stress.

Liu L, Veis J, Reiter W, Motari E, Costello C, Samuelson J J Fungi (Basel). 2021; 7(10).

PMID: 34682295 PMC: 8541566. DOI: 10.3390/jof7100874.

Complex Mechanisms of Antimony Genotoxicity in Budding Yeast Involves Replication and Topoisomerase I-Associated DNA Lesions, Telomere Dysfunction and Inhibition of DNA Repair.

Litwin I, Mucha S, Pilarczyk E, Wysocki R, Maciaszczyk-Dziubinska E Int J Mol Sci. 2021; 22(9).

PMID: 33925940 PMC: 8123508. DOI: 10.3390/ijms22094510.

Tel1 Activation by the MRX Complex Is Sufficient for Telomere Length Regulation but Not for the DNA Damage Response in .

Keener R, Connelly C, Greider C Genetics. 2019; 213(4):1271-1288.

PMID: 31645360 PMC: 6893380. DOI: 10.1534/genetics.119.302713.

Structural basis of allosteric regulation of Tel1/ATM kinase.

Xin J, Xu Z, Wang X, Tian Y, Zhang Z, Cai G Cell Res. 2019; 29(8):655-665.

PMID: 31097817 PMC: 6796912. DOI: 10.1038/s41422-019-0176-1.

The RNA binding protein Npl3 promotes resection of DNA double-strand breaks by regulating the levels of Exo1.

Colombo C, Trovesi C, Menin L, Longhese M, Clerici M Nucleic Acids Res. 2017; 45(11):6530-6545.

PMID: 28472517 PMC: 5499764. DOI: 10.1093/nar/gkx347.

References

Rouse J, Jackson S . Lcd1p recruits Mec1p to DNA lesions in vitro and in vivo. Mol Cell. 2002; 9(4):857-69. DOI: 10.1016/s1097-2765(02)00507-5. View

Cortez D, Guntuku S, Qin J, Elledge S . ATR and ATRIP: partners in checkpoint signaling. Science. 2001; 294(5547):1713-6. DOI: 10.1126/science.1065521. View

Taylor A, Rosney C, Campbell J . Unusual sensitivity of ataxia telangiectasia cells to bleomycin. Cancer Res. 1979; 39(3):1046-50. View

Lehmann A, Stevens S . The response of ataxia telangiectasia cells to bleomycin. Nucleic Acids Res. 1979; 6(5):1953-60. PMC: 327823. DOI: 10.1093/nar/6.5.1953. View

Moore C . Internucleosomal cleavage and chromosomal degradation by bleomycin and phleomycin in yeast. Cancer Res. 1988; 48(23):6837-43. View

Gietz R, Sugino A . New yeast-Escherichia coli shuttle vectors constructed with in vitro mutagenized yeast genes lacking six-base pair restriction sites. Gene. 1988; 74(2):527-34. DOI: 10.1016/0378-1119(88)90185-0. View

Sikorski R, Hieter P . A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae. Genetics. 1989; 122(1):19-27. PMC: 1203683. DOI: 10.1093/genetics/122.1.19. View

Siede W, Friedberg A, Friedberg E . RAD9-dependent G1 arrest defines a second checkpoint for damaged DNA in the cell cycle of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1993; 90(17):7985-9. PMC: 47272. DOI: 10.1073/pnas.90.17.7985. View

Koy J, Pleninger P, Wall L, Pramanik A, Martinez M, Moore C . Genetic changes and bioassays in bleomycin- and phleomycin-treated cells, and their relationship to chromosomal breaks. Mutat Res. 1995; 336(1):19-27. DOI: 10.1016/0921-8777(94)00040-d. View

10.

Wach A, Brachat A, Pohlmann R, Philippsen P . New heterologous modules for classical or PCR-based gene disruptions in Saccharomyces cerevisiae. Yeast. 1994; 10(13):1793-808. DOI: 10.1002/yea.320101310. View

11.

Morrow D, Tagle D, Shiloh Y, Collins F, Hieter P . TEL1, an S. cerevisiae homolog of the human gene mutated in ataxia telangiectasia, is functionally related to the yeast checkpoint gene MEC1. Cell. 1995; 82(5):831-40. DOI: 10.1016/0092-8674(95)90480-8. View

12.

Paulovich A, Hartwell L . A checkpoint regulates the rate of progression through S phase in S. cerevisiae in response to DNA damage. Cell. 1995; 82(5):841-7. DOI: 10.1016/0092-8674(95)90481-6. View

13.

Sanchez Y, Desany B, Jones W, Liu Q, Wang B, Elledge S . Regulation of RAD53 by the ATM-like kinases MEC1 and TEL1 in yeast cell cycle checkpoint pathways. Science. 1996; 271(5247):357-60. DOI: 10.1126/science.271.5247.357. View

14.

Sun Z, Fay D, Marini F, Foiani M, Stern D . Spk1/Rad53 is regulated by Mec1-dependent protein phosphorylation in DNA replication and damage checkpoint pathways. Genes Dev. 1996; 10(4):395-406. DOI: 10.1101/gad.10.4.395. View

15.

Elledge S . Cell cycle checkpoints: preventing an identity crisis. Science. 1996; 274(5293):1664-72. DOI: 10.1126/science.274.5293.1664. View

16.

Paulovich A, Margulies R, Garvik B, Hartwell L . RAD9, RAD17, and RAD24 are required for S phase regulation in Saccharomyces cerevisiae in response to DNA damage. Genetics. 1997; 145(1):45-62. PMC: 1207783. DOI: 10.1093/genetics/145.1.45. View

17.

Carney J, Maser R, Olivares H, Davis E, LE BEAU M, Yates 3rd J . The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response. Cell. 1998; 93(3):477-86. DOI: 10.1016/s0092-8674(00)81175-7. View

18.

Banin S, Moyal L, Shieh S, Taya Y, Anderson C, Chessa L . Enhanced phosphorylation of p53 by ATM in response to DNA damage. Science. 1998; 281(5383):1674-7. DOI: 10.1126/science.281.5383.1674. View

19.

Canman C, Lim D, Cimprich K, Taya Y, Tamai K, Sakaguchi K . Activation of the ATM kinase by ionizing radiation and phosphorylation of p53. Science. 1998; 281(5383):1677-9. DOI: 10.1126/science.281.5383.1677. View

20.

Longhese M, Foiani M, Muzi-Falconi M, Lucchini G, Plevani P . DNA damage checkpoint in budding yeast. EMBO J. 1998; 17(19):5525-8. PMC: 1170880. DOI: 10.1093/emboj/17.19.5525. View