Pratima Sinha
Professor, Biochemistry


Research interest

We are studying mcm (minichromosome maintenance) mutants of yeast whichdestabilize small circular minichromosomes, each carrying an ARS(autonomously replicating sequence) and CEN (centromere) DNA. It wasexpected that these mutants would carry lesions in genes whose products act in trans at ARS or CEN sequences of minichromosomal DNA to impair its replication and/or segregation. This search, in earlier work, had identified many genes which affect DNA replication. We have been working with these mutants, with emphasis on one mutant, mcm2. Using mitotic stability assays we have shown that this mutant affects plasmid and chromosomal DNA replication by causing underinitiations at their replication origins, leading to DNA damage at chromosomes and their subsequent loss from the cells.

We have also undertaken a study of other mcm mutants which do not affectDNA replication. We have cloned several MCM (MCM16, MCM17, MCM18, MCM19,MCM21 and MCM22) genes which belong to the ARS-nonspecific class of MCM mutants. We have shown that all of these genes are required for chromosome segregation. MCM17 is the same as CHL4/CTF17 and MCM18 defines the same ORF as CTF19. Further work is directed towards the characterzation of these genes to determine the molecular mechanisms which govern chromosome stability in yeast.

Important publications (eight)

1. Ghosh SK, Poddar A, Hajra S, Sanyal K, Sinha P (2001) The IML3/MCM19 gene of S. cerevisiae is required for a kinetochore related process of chromosome segregation. Mol. Gen. Genet. (in press).
2. Poddar A, Roy N. and Sinha P. (1999) MCM21 and MCM22, two novel genes of theyeast Saccharomyces cerevisiae are required for chromosome transmission. Molecular Microbiology 31:349-360.
3. Sanyal K., Ghosh S.K. and Sinha P. (1998) The MCM16 gene of the yeast Saccharomyces cerevisiae is required for chromosome segregation, Mol. Gen. Genet 260:242-250.
4. Gangopadhyay S.S., Ray S.S., Sinha P. and Lohia A. (1997) Unusual genomeorganisation in Entamoeba histolytica leads to two overlapping transcripts. Mol. Biochem. Parasitol. 89:73-83.
5. Roy N, Poddar A, Lohia A and Sinha P. (1997) The mcm17 mutation of yeast shows size-dependent segregational defect of a minichromosome. Curr. Genet. 32:182-189.
6. Ray A. and Sinha P. (1995) The mcm2 mutant of yeast causes DNA damage with a requirement of RAD9 for repair. Curr. Genet. 27:95-101.
7. Ray A., Roy N., Maitra M. and Sinha P. (1994). A 61 kb ring chromosome shows ARS-dependent chromosome changes in its mitotic stability in mcm2 mutant of yeast. Curr. Genet. 26:403-409
8. Maiti A.K. and Sinha P. 1992. The mcm2 mutation of yeast affects replication rather than segregation or amplification of the two micron plasmid of yeast. J. Mol. Biol. 224: 545-558.

For M. Sc (II) students of Biophysics, Molecular Biology and Genetics Dept., Calcutta Univ. Rajabazar[the review by L. Guarente on Synthetic enhancement in gene interaction (Trends in Genetics, 1993, vol. 9, 362-366).]