HJURP antagonizes CENP-A mislocalization driven by the H3.3 chaperones HIRA and DAXX.
The centromere specific histone H3 variant CENP-A/CENH3 specifies where the kinetochore is formed in most eukaryotes. Despite tight regulation of CENP-A levels in normal cells, overexpression of CENP-A is a feature shared by various types of solid tumors and results in its mislocalization to non-cen...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2018-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC6203356?pdf=render |
| _version_ | 1811321529102761984 |
|---|---|
| author | Jonathan Nye David Sturgill Rajbir Athwal Yamini Dalal |
| author_facet | Jonathan Nye David Sturgill Rajbir Athwal Yamini Dalal |
| author_sort | Jonathan Nye |
| collection | DOAJ |
| description | The centromere specific histone H3 variant CENP-A/CENH3 specifies where the kinetochore is formed in most eukaryotes. Despite tight regulation of CENP-A levels in normal cells, overexpression of CENP-A is a feature shared by various types of solid tumors and results in its mislocalization to non-centromeric DNA. How CENP-A is assembled ectopically and the consequences of this mislocalization remain topics of high interest. Here, we report that in human colon cancer cells, the H3.3 chaperones HIRA and DAXX promote ectopic CENP-A deposition. Moreover, the correct balance between levels of the centromeric chaperone HJURP and CENP-A is essential to preclude ectopic assembly by H3.3 chaperones. In addition, we find that ectopic localization can recruit kinetochore components, and correlates with mitotic defects and DNA damage in G1 phase. Finally, CENP-A occupancy at the 8q24 locus is also correlated with amplification and overexpression of the MYC gene within that locus. Overall, these data provide insights into the causes and consequences of histone variant mislocalization in human cancer cells. |
| first_indexed | 2024-04-13T13:19:38Z |
| format | Article |
| id | doaj.art-4455b3002cfe47a594a50ec29eaf44cb |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T13:19:38Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-4455b3002cfe47a594a50ec29eaf44cb2022-12-22T02:45:22ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-011310e020594810.1371/journal.pone.0205948HJURP antagonizes CENP-A mislocalization driven by the H3.3 chaperones HIRA and DAXX.Jonathan NyeDavid SturgillRajbir AthwalYamini DalalThe centromere specific histone H3 variant CENP-A/CENH3 specifies where the kinetochore is formed in most eukaryotes. Despite tight regulation of CENP-A levels in normal cells, overexpression of CENP-A is a feature shared by various types of solid tumors and results in its mislocalization to non-centromeric DNA. How CENP-A is assembled ectopically and the consequences of this mislocalization remain topics of high interest. Here, we report that in human colon cancer cells, the H3.3 chaperones HIRA and DAXX promote ectopic CENP-A deposition. Moreover, the correct balance between levels of the centromeric chaperone HJURP and CENP-A is essential to preclude ectopic assembly by H3.3 chaperones. In addition, we find that ectopic localization can recruit kinetochore components, and correlates with mitotic defects and DNA damage in G1 phase. Finally, CENP-A occupancy at the 8q24 locus is also correlated with amplification and overexpression of the MYC gene within that locus. Overall, these data provide insights into the causes and consequences of histone variant mislocalization in human cancer cells.http://europepmc.org/articles/PMC6203356?pdf=render |
| spellingShingle | Jonathan Nye David Sturgill Rajbir Athwal Yamini Dalal HJURP antagonizes CENP-A mislocalization driven by the H3.3 chaperones HIRA and DAXX. PLoS ONE |
| title | HJURP antagonizes CENP-A mislocalization driven by the H3.3 chaperones HIRA and DAXX. |
| title_full | HJURP antagonizes CENP-A mislocalization driven by the H3.3 chaperones HIRA and DAXX. |
| title_fullStr | HJURP antagonizes CENP-A mislocalization driven by the H3.3 chaperones HIRA and DAXX. |
| title_full_unstemmed | HJURP antagonizes CENP-A mislocalization driven by the H3.3 chaperones HIRA and DAXX. |
| title_short | HJURP antagonizes CENP-A mislocalization driven by the H3.3 chaperones HIRA and DAXX. |
| title_sort | hjurp antagonizes cenp a mislocalization driven by the h3 3 chaperones hira and daxx |
| url | http://europepmc.org/articles/PMC6203356?pdf=render |
| work_keys_str_mv | AT jonathannye hjurpantagonizescenpamislocalizationdrivenbytheh33chaperoneshiraanddaxx AT davidsturgill hjurpantagonizescenpamislocalizationdrivenbytheh33chaperoneshiraanddaxx AT rajbirathwal hjurpantagonizescenpamislocalizationdrivenbytheh33chaperoneshiraanddaxx AT yaminidalal hjurpantagonizescenpamislocalizationdrivenbytheh33chaperoneshiraanddaxx |