Our goal is to dissect the mechanism by which kinetochore proteins binds the centromeric chromatin in the genome and creates the basis for a functional centromere. Since the project started by new postdoctoral associate in 2010, this work is in progress. A separate study was conducted in collaboration with a human pluripotent cell (hPSC) investigator Amander Clark (UCLA), where we discovered that the centromeric protein reserve plays a role in cell differentiation and in chromosome damage sensing. This work was published in Human Mol. Genetics August 2010. The follow up project was suspended due to the recent ruling on the use of hPSC in federally funded projects. We have followed up on this project using senescent human cells wherein we find that CENP-A appears to remain active despite the lack of cell cycle activity. We are now investigating, if, like in cancer cells (Gill et al, in review;and Ambartyasuman et al 2010), CENP-A plays an ectopic role in these cells.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011209-05
Application #
8763401
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2013
Total Cost
$200,643
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Quénet, Delphine; Dalal, Yamini (2015) Correction: a long non-coding RNA is required for targeting centromeric protein A to the human centromere. Elife 4:
Dalal, Yamini; McNally, James G (2014) Now you see it, now you don't: a biochemist's primer for advances in high-resolution microscopy: comment on ""Biomolecular dynamics and binding studies in the living cell"" by Stephan Diekmann and Christian Hoischen. Phys Life Rev 11:36-7; discussion 38
Volle, Catherine; Dalal, Yamini (2014) Histone variants: the tricksters of the chromatin world. Curr Opin Genet Dev 25:8-14,138
Bui, Minh; Walkiewicz, Marcin P; Dimitriadis, Emilios K et al. (2013) The CENP-A nucleosome: a battle between Dr Jekyll and Mr Hyde. Nucleus 4:37-42
Quénet, Delphine; Dalal, Yamini (2012) The CENP-A nucleosome: a dynamic structure and role at the centromere. Chromosome Res 20:465-79
Quénet, Delphine; McNally, James G; Dalal, Yamini (2012) Through thick and thin: the conundrum of chromatin fibre folding in vivo. EMBO Rep 13:943-4
Dalal, Yamini; Bui, Minh (2010) Down the rabbit hole of centromere assembly and dynamics. Curr Opin Cell Biol 22:392-402
Ambartsumyan, Gayane; Gill, Rajbir K; Perez, Silvia Diaz et al. (2010) Centromere protein A dynamics in human pluripotent stem cell self-renewal, differentiation and DNA damage. Hum Mol Genet 19:3970-82
Dimitriadis, Emilios K; Weber, Christian; Gill, Rajbir K et al. (2010) Tetrameric organization of vertebrate centromeric nucleosomes. Proc Natl Acad Sci U S A 107:20317-22