Publications by authors named "Arunika Das"

6 Publications

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Maternal inheritance of centromeres through the germline.

Curr Top Dev Biol 2020 25;140:35-54. Epub 2020 Apr 25.

Department of Biology, University of Pennsylvania, Philadelphia, PA, United States. Electronic address:

The centromere directs chromosome segregation but is not itself genetically encoded. In most species, centromeres are epigenetically defined by the presence of a histone H3 variant CENP-A, independent of the underlying DNA sequence. Therefore, to maintain centromeres and ensure accurate chromosome segregation, CENP-A nucleosomes must be inherited across generations through the germline. In this chapter we discuss three aspects of maternal centromere inheritance. First, we propose mechanisms for maintaining CENP-A nucleosomes through the prolonged prophase arrest in mammalian oocytes. Second, we review mechanisms by which selfish centromeres bias their transmission through female meiosis. Third, we discuss regulation of centromere size through early embryonic development.
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http://dx.doi.org/10.1016/bs.ctdb.2020.03.004DOI Listing
April 2020

Sister centromere fusion during meiosis I depends on maintaining cohesins and destabilizing microtubule attachments.

PLoS Genet 2019 05 31;15(5):e1008072. Epub 2019 May 31.

Waksman Institute and Department of Genetics, Rutgers, the State University of New Jersey, Piscataway, New Jersey, United States of America.

Sister centromere fusion is a process unique to meiosis that promotes co-orientation of the sister kinetochores, ensuring they attach to microtubules from the same pole during metaphase I. We have found that the kinetochore protein SPC105R/KNL1 and Protein Phosphatase 1 (PP1-87B) regulate sister centromere fusion in Drosophila oocytes. The analysis of these two proteins, however, has shown that two independent mechanisms maintain sister centromere fusion. Maintenance of sister centromere fusion by SPC105R depends on Separase, suggesting cohesin proteins must be maintained at the core centromeres. In contrast, maintenance of sister centromere fusion by PP1-87B does not depend on either Separase or WAPL. Instead, PP1-87B maintains sister centromeres fusion by regulating microtubule dynamics. We demonstrate that this regulation is through antagonizing Polo kinase and BubR1, two proteins known to promote stability of kinetochore-microtubule (KT-MT) attachments, suggesting that PP1-87B maintains sister centromere fusion by inhibiting stable KT-MT attachments. Surprisingly, C(3)G, the transverse element of the synaptonemal complex (SC), is also required for centromere separation in Pp1-87B RNAi oocytes. This is evidence for a functional role of centromeric SC in the meiotic divisions, that might involve regulating microtubule dynamics. Together, we propose two mechanisms maintain co-orientation in Drosophila oocytes: one involves SPC105R to protect cohesins at sister centromeres and another involves PP1-87B to regulate spindle forces at end-on attachments.
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http://dx.doi.org/10.1371/journal.pgen.1008072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6581285PMC
May 2019

Keeping Parents Apart.

Dev Cell 2018 08;46(3):255-256

Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:

Parental genomes are initially separate in the zygote following fertilization. A recent study in Science by Reichmann et al. (2018) reveals that dual spindles assemble around the two pronuclei in mouse embryos to maintain separation of the two parental genomes through the first zygotic division.
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http://dx.doi.org/10.1016/j.devcel.2018.07.019DOI Listing
August 2018

Kinesin 6 Regulation in Female Meiosis by the Non-conserved N- and C- Terminal Domains.

G3 (Bethesda) 2018 05 4;8(5):1555-1569. Epub 2018 May 4.

Waksman Institute, Rutgers, the State University of New Jersey, NJ-08854

Bipolar spindle assembly occurs in the absence of centrosomes in the oocytes of most organisms. In the absence of centrosomes in oocytes, we have proposed that the kinesin 6 Subito, a MKLP-2 homolog, is required for establishing spindle bipolarity and chromosome biorientation by assembling a robust central spindle during prometaphase I. Although the functions of the conserved motor domains of kinesins is well studied, less is known about the contribution of the poorly conserved N- and C- terminal domains to motor function. In this study, we have investigated the contribution of these domains to kinesin 6 functions in meiosis and early embryonic development. We found that the N-terminal domain has antagonistic elements that regulate localization of the motor to microtubules. Other parts of the N- and C-terminal domains are not required for microtubule localization but are required for motor function. Some of these elements of Subito are more important for either mitosis or meiosis, as revealed by separation-of-function mutants. One of the functions for both the N- and C-terminals domains is to restrict the CPC to the central spindle in a ring around the chromosomes. We also provide evidence that CDK1 phosphorylation of Subito regulates its activity associated with homolog bi-orientation. These results suggest the N- and C-terminal domains of Subito, while not required for localization to the central spindle microtubules, have important roles regulating Subito, by interacting with other spindle proteins and promoting activities such as bipolar spindle formation and homologous chromosome bi-orientation during meiosis.
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http://dx.doi.org/10.1534/g3.117.300571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5940148PMC
May 2018

Centromere inheritance through the germline.

Chromosoma 2017 Oct 8;126(5):595-604. Epub 2017 Aug 8.

Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA, 19104, USA.

The centromere directs chromosome segregation and genetic inheritance but is not itself heritable in a canonical, DNA-based manner. In most species, centromeres are epigenetically defined by the presence of a histone H3 variant centromere protein A (CENP-A), independent of underlying DNA sequence. Therefore, centromere inheritance depends on maintaining the CENP-A nucleosome mark across generations. Experiments in cycling somatic cells have led to a model in which centromere identity is maintained by a cell cycle-coupled CENP-A chromatin assembly pathway. However, the processes of animal gametogenesis pose unique challenges to centromere inheritance because of the extended cell cycle arrest and the massive genome reorganization in the female and male germline, respectively. Here, we review our current understanding of germline centromere inheritance and highlight outstanding questions.
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http://dx.doi.org/10.1007/s00412-017-0640-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5693723PMC
October 2017

Spindle Assembly and Chromosome Segregation Requires Central Spindle Proteins in Drosophila Oocytes.

Genetics 2016 Jan 12;202(1):61-75. Epub 2015 Nov 12.

Waksman Institute, Rutgers, The State University of New Jersey, New Jersey 08854 Department of Genetics, Rutgers, The State University of New Jersey, New Jersey 08854

Oocytes segregate chromosomes in the absence of centrosomes. In this situation, the chromosomes direct spindle assembly. It is still unclear in this system which factors are required for homologous chromosome bi-orientation and spindle assembly. The Drosophila kinesin-6 protein Subito, although nonessential for mitotic spindle assembly, is required to organize a bipolar meiotic spindle and chromosome bi-orientation in oocytes. Along with the chromosomal passenger complex (CPC), Subito is an important part of the metaphase I central spindle. In this study we have conducted genetic screens to identify genes that interact with subito or the CPC component Incenp. In addition, the meiotic mutant phenotype for some of the genes identified in these screens were characterized. We show, in part through the use of a heat-shock-inducible system, that the Centralspindlin component RacGAP50C and downstream regulators of cytokinesis Rho1, Sticky, and RhoGEF2 are required for homologous chromosome bi-orientation in metaphase I oocytes. This suggests a novel function for proteins normally involved in mitotic cell division in the regulation of microtubule-chromosome interactions. We also show that the kinetochore protein, Polo kinase, is required for maintaining chromosome alignment and spindle organization in metaphase I oocytes. In combination our results support a model where the meiotic central spindle and associated proteins are essential for acentrosomal chromosome segregation.
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http://dx.doi.org/10.1534/genetics.115.181081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4701103PMC
January 2016