Department of Biochemistry

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Browsing Department of Biochemistry by Author "Abraham, Neethu Maria"
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    Elevated dosage of Ulp1 disrupts telomeric silencing in Saccharomyces cerevisiae
    ( 2018-12-01) Abraham, Neethu Maria ; Mishra, Krishnaveni
    Heterochromatin in Saccharomyces cerevisiae is found at the telomeres and silent mating type loci. Many sub-telomeric loci are naturally silenced by this mechanism. In addition, when euchromatic genes are placed proximal to telomeric repeats they are subjected to heritable gene silencing that is referred to as telomere position effect. Establishment and maintenance of TPE is dependent on the assembly of silent information regulator proteins at these loci. Here we show that dosage of SUMO isopeptidase, Ulp1, is important for regulation of TPE. Moderate elevation of Ulp1 reduces silencing of both, the euchromatic gene placed proximal to telomeric repeats and the sub-telomeric genes that are silenced by TPE. We further demonstrate that this loss in silencing is due to reduced recruitment of one of the silent information regulators, Sir3p. We show that SUMO peptidase, Ulp1, regulates telomeric position effect by regulating the recruitment of Sir proteins.
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    Siz2 prevents ribosomal dna recombination by modulating levels of Tof2 in Saccharomyces cerevisiae
    ( 2019-01-01) Abraham, Neethu Maria ; Ramalingam, Kathirvel ; Murthy, Saketh ; Mishra, Krishnaveni
    Ribosomal DNA (rDNA) recombination in budding yeast is regulated by multiple converging processes, including posttranslational modifications such as SUMOylation. In this study, we report that the absence of a SUMO E3 ligase, Siz2, results in increased unequal rDNA exchange. Weshow that Siz2 is enriched at the replication fork barrier (RFB) in the rDNA and also controlsthe homeostasis of Tof2 protein.siz2▵ resulted in increased accumulation of total Tof2 in thecell and a consequent increase in the enrichment of Tof2 at the rDNA. Overproducing Tof2 ectopically or conditional overexpression of Tof2 also resulted in higher levels of rDNA recombination, suggesting a direct role for Tof2. Additionally, our chromatin immunoprecipitation(ChIP) data indicate that the accumulation of Tof2 in a siz2▵ mutant resulted in an enhanced association of Fob1, an RFB binding protein at the rDNA at the RFB. This increased Fob1 association at the RFB may have resulted in the elevated rDNA recombination. Our study thus demonstrates that the Tof2 levels modulate recombination at the rDNA.
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    Sumoylation of Sir2 differentially regulates transcriptional silencing in yeast
    ( 2015-01-01) Hannan, Abdul ; Abraham, Neethu Maria ; Goyal, Siddharth ; Jamir, Imlitoshi ; Priyakumar, U. Deva ; Mishra, Krishnaveni
    Silent information regulator 2 (Sir2), the founding member of the conserved sirtuin family of NAD+- dependent histone deacetylase, regulates several physiological processes including genome stability, gene silencing, metabolism and life span in yeast. Within the nucleus, Sir2 is associated with telomere clusters in the nuclear periphery and rDNA in the nucleolus and regulates gene silencing at these genomic sites. How distribution of Sir2 between telomere and rDNA is regulated is not known. Here we show that Sir2 is sumoylated and this modification modulates the intra-nuclear distribution of Sir2. We identify Siz2 as the key SUMO ligase and show that multiple lysines in Sir2 are subject to this sumoylation activity. Mutating K215 alone counteracts the inhibitory effect of Siz2 on telomeric silencing. SUMO modification of Sir2 impairs interaction with Sir4 but not Net1 and, furthermore, SUMO modified Sir2 shows predominant nucleolar localization. Our findings demonstrate that sumoylation of Sir2 modulates distribution between telomeres and rDNA and this is likely to have implications for Sir2 function in other loci as well.