TY - JOUR
T1 - Nanoscale dynamics of centromere nucleosomes and the critical roles of CENP-A
AU - Stumme-Diers, Micah P.
AU - Banerjee, Siddhartha
AU - Hashemi, Mohtadin
AU - Sun, Zhiqiang
AU - Lyubchenko, Yuri L.
N1 - Funding Information:
We thank Yamini Dalal for the gift of recombinant histones, training, enthusiastic feedback, and critical review of the manuscript. We acknowledge Daniel Melters (Dalal lab) for thoughtful discussions and critical review of the manuscript. National Science Foundation [MCB 1515346 to Y.L.L.]; National Institutes of Health [GM096039 and GM118006 both to Y.L.L.]; M.H. was partially supported by the Bukey Memorial Fellowship. Funding for open access charge: National Science Foundation [MCB 1515346 to Y.L.L.].
Funding Information:
National Science Foundation [MCB 1515346 to Y.L.L.]; National Institutes of Health [GM096039 and GM118006 both to Y.L.L.]; M.H. was partially supported by the Bukey Memorial Fellowship. Funding for open access charge: National Science Foundation [MCB 1515346 to Y.L.L.]. Conflict of interest statement. None declared.
Publisher Copyright:
© The Author(s) 2017.
PY - 2018/1/9
Y1 - 2018/1/9
N2 - In the absence of a functioning centromere, chromosome segregation becomes aberrant, leading to an increased rate of aneuploidy. The highly specific recognition of centromeres by kinetochores suggests that specific structural characteristics define this region, however, the structural details and mechanism underlying this recognition remains a matter of intense investigation. To address this, high-speed atomic force microscopy was used for direct visualization of the spontaneous dynamics of CENP-A nucleosomes at the sub-second time scale. We report that CENP-A nucleosomes change conformation spontaneously and reversibly, utilizing two major pathways: unwrapping, and looping of the DNA; enabling core transfer between neighboring DNA substrates. Along with these nucleosome dynamics we observed that CENP-A stabilizes the histone core against dissociating to histone subunits upon unwrapping DNA, unique from H3 cores which are only capable of such plasticity in the presence of remodeling factors. These findings have implications for the dynamics and integrity of nucleosomes at the centromere.
AB - In the absence of a functioning centromere, chromosome segregation becomes aberrant, leading to an increased rate of aneuploidy. The highly specific recognition of centromeres by kinetochores suggests that specific structural characteristics define this region, however, the structural details and mechanism underlying this recognition remains a matter of intense investigation. To address this, high-speed atomic force microscopy was used for direct visualization of the spontaneous dynamics of CENP-A nucleosomes at the sub-second time scale. We report that CENP-A nucleosomes change conformation spontaneously and reversibly, utilizing two major pathways: unwrapping, and looping of the DNA; enabling core transfer between neighboring DNA substrates. Along with these nucleosome dynamics we observed that CENP-A stabilizes the histone core against dissociating to histone subunits upon unwrapping DNA, unique from H3 cores which are only capable of such plasticity in the presence of remodeling factors. These findings have implications for the dynamics and integrity of nucleosomes at the centromere.
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U2 - 10.1093/nar/gkx933
DO - 10.1093/nar/gkx933
M3 - Article
C2 - 29040671
AN - SCOPUS:85045927524
VL - 46
SP - 94
EP - 103
JO - Nucleic Acids Research
JF - Nucleic Acids Research
SN - 0305-1048
IS - 1
ER -