Mcm10 Mediates the Interaction Between DNA Replication and Silencing Machineries

Overview

Journal Genetics

Publisher Oxford University Press

Specialty Genetics

Date 2008 Dec 10

PMID 19064704

Citations 20

Authors

Ivan Liachko

Bik K Tye

Affiliations

Soon will be listed here.

Abstract

The connection between DNA replication and heterochromatic silencing in yeast has been a topic of investigation for >20 years. While early studies showed that silencing requires passage through S phase and implicated several DNA replication factors in silencing, later works showed that silent chromatin could form without DNA replication. In this study we show that members of the replicative helicase (Mcm3 and Mcm7) play a role in silencing and physically interact with the essential silencing factor, Sir2, even in the absence of DNA replication. Another replication factor, Mcm10, mediates the interaction between these replication and silencing proteins via a short C-terminal domain. Mutations in this region of Mcm10 disrupt the interaction between Sir2 and several of the Mcm2-7 proteins. While such mutations caused silencing defects, they did not cause DNA replication defects or affect the association of Sir2 with chromatin. Our findings suggest that Mcm10 is required for the coupling of the replication and silencing machineries to silence chromatin in a context outside of DNA replication beyond the recruitment and spreading of Sir2 on chromatin.

Citing Articles

Multifaceted role of the DNA replication protein MCM10 in maintaining genome stability and its implication in human diseases.

Ahmed S, Sasikumar J, Laha S, Das S Cancer Metastasis Rev. 2024; 43(4):1353-1371.

PMID: 39240414 DOI: 10.1007/s10555-024-10209-3.

The interaction networks of the budding yeast and human DNA replication-initiation proteins.

Wu R, Amin A, Wang Z, Huang Y, Man-Hei Cheung M, Yu Z Cell Cycle. 2019; 18(6-7):723-741.

PMID: 30890025 PMC: 6464591. DOI: 10.1080/15384101.2019.1586509.

Modulation of Gene Silencing by Cdc7p via H4 K16 Acetylation and Phosphorylation of Chromatin Assembly Factor CAF-1 in .

Young T, Cui Y, Irudayaraj J, Kirchmaier A Genetics. 2019; 211(4):1219-1237.

PMID: 30728156 PMC: 6456304. DOI: 10.1534/genetics.118.301858.

Novel roles of HP1a and Mcm10 in DNA replication, genome maintenance and photoreceptor cell differentiation.

Vo N, Suong D, Yoshino N, Yoshida H, Cotterill S, Yamaguchi M Nucleic Acids Res. 2017; 45(3):1233-1254.

PMID: 28180289 PMC: 5388399. DOI: 10.1093/nar/gkw1174.

Establishment of expression-state boundaries by Rif1 and Taz1 in fission yeast.

Toteva T, Mason B, Kanoh Y, Brogger P, Green D, Verhein-Hansen J Proc Natl Acad Sci U S A. 2017; 114(5):1093-1098.

PMID: 28096402 PMC: 5293076. DOI: 10.1073/pnas.1614837114.

References

McNally F, Rine J . A synthetic silencer mediates SIR-dependent functions in Saccharomyces cerevisiae. Mol Cell Biol. 1991; 11(11):5648-59. PMC: 361936. DOI: 10.1128/mcb.11.11.5648-5659.1991. View

Liachko I, Tye B . Mcm10 is required for the maintenance of transcriptional silencing in Saccharomyces cerevisiae. Genetics. 2005; 171(2):503-15. PMC: 1456767. DOI: 10.1534/genetics.105.042333. View

Dziak R, Leishman D, Radovic M, Tye B, Yankulov K . Evidence for a role of MCM (mini-chromosome maintenance)5 in transcriptional repression of sub-telomeric and Ty-proximal genes in Saccharomyces cerevisiae. J Biol Chem. 2003; 278(30):27372-81. DOI: 10.1074/jbc.M301110200. View

Triolo T, Sternglanz R . Role of interactions between the origin recognition complex and SIR1 in transcriptional silencing. Nature. 1996; 381(6579):251-3. DOI: 10.1038/381251a0. View

Douglas N, Dozier S, Donato J . Dual roles for Mcm10 in DNA replication initiation and silencing at the mating-type loci. Mol Biol Rep. 2005; 32(4):197-204. DOI: 10.1007/s11033-005-2312-x. View

Crampton A, Chang F, Pappas Jr D, Frisch R, Weinreich M . An ARS element inhibits DNA replication through a SIR2-dependent mechanism. Mol Cell. 2008; 30(2):156-66. DOI: 10.1016/j.molcel.2008.02.019. View

AXELROD A, Rine J . A role for CDC7 in repression of transcription at the silent mating-type locus HMR in Saccharomyces cerevisiae. Mol Cell Biol. 1991; 11(2):1080-91. PMC: 359783. DOI: 10.1128/mcb.11.2.1080-1091.1991. View

Kamakaka R, Rine J . A role for the replication proteins PCNA, RF-C, polymerase epsilon and Cdc45 in transcriptional silencing in Saccharomyces cerevisiae. Genetics. 1999; 153(3):1171-82. PMC: 1460823. DOI: 10.1093/genetics/153.3.1171. View

Pillus L, Rine J . Epigenetic inheritance of transcriptional states in S. cerevisiae. Cell. 1989; 59(4):637-47. DOI: 10.1016/0092-8674(89)90009-3. View

10.

Christensen T, Tye B . Drosophila MCM10 interacts with members of the prereplication complex and is required for proper chromosome condensation. Mol Biol Cell. 2003; 14(6):2206-15. PMC: 194871. DOI: 10.1091/mbc.e02-11-0706. View

11.

Kyrion G, Liu K, Liu C, Lustig A . RAP1 and telomere structure regulate telomere position effects in Saccharomyces cerevisiae. Genes Dev. 1993; 7(7A):1146-59. DOI: 10.1101/gad.7.7a.1146. View

12.

Ricke R, Bielinsky A . A conserved Hsp10-like domain in Mcm10 is required to stabilize the catalytic subunit of DNA polymerase-alpha in budding yeast. J Biol Chem. 2006; 281(27):18414-25. DOI: 10.1074/jbc.M513551200. View

13.

Cook C, Kung G, Peterson F, Volkman B, Lei M . A novel zinc finger is required for Mcm10 homocomplex assembly. J Biol Chem. 2003; 278(38):36051-8. DOI: 10.1074/jbc.M306049200. View

14.

Martins-Taylor K, Dula M, Holmes S . Heterochromatin spreading at yeast telomeres occurs in M phase. Genetics. 2004; 168(1):65-75. PMC: 1448083. DOI: 10.1534/genetics.103.020149. View

15.

Rusche L, Kirchmaier A, Rine J . Ordered nucleation and spreading of silenced chromatin in Saccharomyces cerevisiae. Mol Biol Cell. 2002; 13(7):2207-22. PMC: 117306. DOI: 10.1091/mbc.e02-03-0175. View

16.

Ricke R, Bielinsky A . Mcm10 regulates the stability and chromatin association of DNA polymerase-alpha. Mol Cell. 2004; 16(2):173-85. DOI: 10.1016/j.molcel.2004.09.017. View

17.

Zhang Z, Hayashi M, Merkel O, Stillman B, Xu R . Structure and function of the BAH-containing domain of Orc1p in epigenetic silencing. EMBO J. 2002; 21(17):4600-11. PMC: 125411. DOI: 10.1093/emboj/cdf468. View

18.

Hou Z, Bernstein D, Fox C, Keck J . Structural basis of the Sir1-origin recognition complex interaction in transcriptional silencing. Proc Natl Acad Sci U S A. 2005; 102(24):8489-94. PMC: 1150864. DOI: 10.1073/pnas.0503525102. View

19.

Homesley L, Lei M, Kawasaki Y, Sawyer S, Christensen T, Tye B . Mcm10 and the MCM2-7 complex interact to initiate DNA synthesis and to release replication factors from origins. Genes Dev. 2000; 14(8):913-26. PMC: 316538. View

20.

Lee J, Seo Y, Hurwitz J . The Cdc23 (Mcm10) protein is required for the phosphorylation of minichromosome maintenance complex by the Dfp1-Hsk1 kinase. Proc Natl Acad Sci U S A. 2003; 100(5):2334-9. PMC: 151341. DOI: 10.1073/pnas.0237384100. View