Abstract

We have intrinsic properties of components of human centromeres, finding them to be surprisingly elastic. These elastic components become rigidified when incorporated into active kinetochores, and suppress centromeric accessibility, thereby suppressing transcription. These data have massive consequences for translocations in cancer cells where we have mapped centromere-like domains in euchromatin, which are sites of fragility. The current focus is to establish whether centromere-like domains in fragile sites can alter the structural stability of those sites.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011207-11
Application #
10014571
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
2019
Total Cost
Indirect Cost

  Institution

Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Nuccio, A G; Bui, M; Dalal, Y et al. (2017) Mass Spectrometry-Based Methodology for Identification of Native Histone Variant Modifications From Mammalian Tissues and Solid Tumors. Methods Enzymol 586:275-290
Vlijm, R; Kim, S H; De Zwart, P L et al. (2017) The supercoiling state of DNA determines the handedness of both H3 and CENP-A nucleosomes. Nanoscale 9:1862-1870
Bui, Minh; Pitman, Mary; Nuccio, Arthur et al. (2017) Internal modifications in the CENP-A nucleosome modulate centromeric dynamics. Epigenetics Chromatin 10:17
Zhao, Haiqing; Winogradoff, David; Bui, Minh et al. (2016) Promiscuous Histone Mis-Assembly Is Actively Prevented by Chaperones. J Am Chem Soc 138:13207-13218
Kim, Sung Hyun; Vlijm, Rifka; van der Torre, Jaco et al. (2016) CENP-A and H3 Nucleosomes Display a Similar Stability to Force-Mediated Disassembly. PLoS One 11:e0165078
Quénet, D; Sturgill, D; Dalal, Y (2016) Identifying Centromeric RNAs Involved in Histone Dynamics In Vivo. Methods Enzymol 573:445-66
Winogradoff, David; Zhao, Haiqing; Dalal, Yamini et al. (2015) Shearing of the CENP-A dimerization interface mediates plasticity in the octameric centromeric nucleosome. Sci Rep 5:17038
Quénet, Delphine; Dalal, Yamini (2015) Correction: a long non-coding RNA is required for targeting centromeric protein A to the human centromere. Elife 4:
Walkiewicz, Marcin P; Dimitriadis, Emilios K; Dalal, Yamini (2014) CENP-A octamers do not confer a reduction in nucleosome height by AFM. Nat Struct Mol Biol 21:2-3
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

Showing the most recent 10 out of 19 publications