Mechanism of Regulation of Intrachromatid Recombination and Long-Range Chromosome Interactions in Saccharomyces cerevisiae

Shamsu Zaman; Malay Choudhury; James C Jiang; Pankaj Srivastava; Bidyut K Mohanty; Christopher Danielson; Sean J Humphrey; S Michal Jazwinski; Deepak Bastia

doi:10.1128/MCB.01100-15

Mechanism of Regulation of Intrachromatid Recombination and Long-Range Chromosome Interactions in Saccharomyces cerevisiae

Mol Cell Biol. 2016 May 2;36(10):1451-63. doi: 10.1128/MCB.01100-15. Print 2016 May 15.

Authors

Shamsu Zaman¹, Malay Choudhury¹, James C Jiang², Pankaj Srivastava¹, Bidyut K Mohanty¹, Christopher Danielson¹, Sean J Humphrey³, S Michal Jazwinski⁴, Deepak Bastia⁵

Affiliations

¹ Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina, USA.
² Department of Medicine and Tulane Center for Aging, Tulane University, New Orleans, Louisiana, USA.
³ Max Planck Institute of Biochemistry, Martinsried, Germany.
⁴ Department of Medicine and Tulane Center for Aging, Tulane University, New Orleans, Louisiana, USA sjazwins@tulane.edu bastia@musc.edu.
⁵ Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina, USA sjazwins@tulane.edu bastia@musc.edu.

Abstract

The NAD-dependent histone deacetylase Sir2 controls ribosomal DNA (rDNA) silencing by inhibiting recombination and RNA polymerase II-catalyzed transcription in the rDNA of Saccharomyces cerevisiae Sir2 is recruited to nontranscribed spacer 1 (NTS1) of the rDNA array by interaction between the RENT ( RE: gulation of N: ucleolar S: ilencing and T: elophase exit) complex and the replication terminator protein Fob1. The latter binds to its cognate sites, called replication termini (Ter) or replication fork barriers (RFB), that are located in each copy of NTS1. This work provides new mechanistic insights into the regulation of rDNA silencing and intrachromatid recombination by showing that Sir2 recruitment is stringently regulated by Fob1 phosphorylation at specific sites in its C-terminal domain (C-Fob1), which also regulates long-range Ter-Ter interactions. We show further that long-range Fob1-mediated Ter-Ter interactions in trans are downregulated by Sir2. These regulatory mechanisms control intrachromatid recombination and the replicative life span (RLS).

MeSH terms

Cell Cycle Proteins / chemistry
Cell Cycle Proteins / metabolism
Chromatids / genetics*
Chromosomes, Fungal / genetics
DNA, Ribosomal / metabolism*
DNA-Binding Proteins / chemistry
DNA-Binding Proteins / metabolism
Down-Regulation
Intracellular Signaling Peptides and Proteins / chemistry
Intracellular Signaling Peptides and Proteins / metabolism
Nuclear Proteins / chemistry
Nuclear Proteins / metabolism
Phosphorylation
Protein Binding
Recombination, Genetic*
Saccharomyces cerevisiae / genetics*
Saccharomyces cerevisiae / metabolism
Saccharomyces cerevisiae Proteins / chemistry
Saccharomyces cerevisiae Proteins / metabolism*
Silent Information Regulator Proteins, Saccharomyces cerevisiae / chemistry
Silent Information Regulator Proteins, Saccharomyces cerevisiae / metabolism
Sirtuin 2 / chemistry
Sirtuin 2 / metabolism

Substances

Cell Cycle Proteins
DNA, Ribosomal
DNA-Binding Proteins
FOB1 protein, S cerevisiae
Intracellular Signaling Peptides and Proteins
Net1 protein, S cerevisiae
Nuclear Proteins
Saccharomyces cerevisiae Proteins
Silent Information Regulator Proteins, Saccharomyces cerevisiae
TOF2 protein, S cerevisiae
SIR2 protein, S cerevisiae
Sirtuin 2

Grants and funding

R37 AG006168/AG/NIA NIH HHS/United States