Dual roles of TRF1 in tethering telomeres to the nuclear envelope and protecting them from fusion during meiosis
Wang, Lina LU ; Tu, Zhaowei ; Liu, Chao ; Liu, Hongbin ; Kaldis, Philipp LU
; Chen, Zijiang
and Li, Wei
LU
(2018)
In Cell Death and Differentiation
25(6).
p.1174-1188
- Abstract
Telomeres integrity is indispensable for chromosomal stability by preventing chromosome erosion and end-to-end fusions. During meiosis, telomeres attach to the inner nuclear envelope and cluster into a highly crowded microenvironment at the bouquet stage, which requires specific mechanisms to protect the telomeres from fusion. Here, we demonstrate that germ cell-specific knockout of a shelterin complex subunit, Trf1, results in arrest of spermatocytes at two different stages. The obliterated telomere-nuclear envelope attachment in Trf1-deficient spermatocytes impairs homologue synapsis and recombination, resulting in a pachytene-like arrest, while the meiotic division arrest might stem from chromosome end-to-end fusion due to the... (More)
Telomeres integrity is indispensable for chromosomal stability by preventing chromosome erosion and end-to-end fusions. During meiosis, telomeres attach to the inner nuclear envelope and cluster into a highly crowded microenvironment at the bouquet stage, which requires specific mechanisms to protect the telomeres from fusion. Here, we demonstrate that germ cell-specific knockout of a shelterin complex subunit, Trf1, results in arrest of spermatocytes at two different stages. The obliterated telomere-nuclear envelope attachment in Trf1-deficient spermatocytes impairs homologue synapsis and recombination, resulting in a pachytene-like arrest, while the meiotic division arrest might stem from chromosome end-to-end fusion due to the failure of recruiting meiosis specific telomere associated proteins. Further investigations uncovered that TRF1 could directly interact with Speedy A, and Speedy A might work as a scaffold protein to further recruit Cdk2, thus protecting telomeres from fusion at this stage. Together, our results reveal a novel mechanism of TRF1, Speedy A, and Cdk2 in protecting telomere from fusion in a highly crowded microenvironment during meiosis.
(Less)
- author
- Wang, Lina
LU
; Tu, Zhaowei
; Liu, Chao
; Liu, Hongbin
; Kaldis, Philipp
LU
; Chen, Zijiang
and Li, Wei
LU
- publishing date
- 2018-06
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Cell Death and Differentiation
- volume
- 25
- issue
- 6
- pages
- 15 pages
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:29311622
- scopus:85047203969
- ISSN
- 1350-9047
- DOI
- 10.1038/s41418-017-0037-8
- language
- English
- LU publication?
- no
- id
- 95b1ad08-83bb-4154-a555-d7b7acb314aa
- date added to LUP
- 2019-09-17 14:47:40
- date last changed
- 2024-10-02 13:07:47
@article{95b1ad08-83bb-4154-a555-d7b7acb314aa,
abstract = {{<p>Telomeres integrity is indispensable for chromosomal stability by preventing chromosome erosion and end-to-end fusions. During meiosis, telomeres attach to the inner nuclear envelope and cluster into a highly crowded microenvironment at the bouquet stage, which requires specific mechanisms to protect the telomeres from fusion. Here, we demonstrate that germ cell-specific knockout of a shelterin complex subunit, Trf1, results in arrest of spermatocytes at two different stages. The obliterated telomere-nuclear envelope attachment in Trf1-deficient spermatocytes impairs homologue synapsis and recombination, resulting in a pachytene-like arrest, while the meiotic division arrest might stem from chromosome end-to-end fusion due to the failure of recruiting meiosis specific telomere associated proteins. Further investigations uncovered that TRF1 could directly interact with Speedy A, and Speedy A might work as a scaffold protein to further recruit Cdk2, thus protecting telomeres from fusion at this stage. Together, our results reveal a novel mechanism of TRF1, Speedy A, and Cdk2 in protecting telomere from fusion in a highly crowded microenvironment during meiosis.</p>}},
author = {{Wang, Lina and Tu, Zhaowei and Liu, Chao and Liu, Hongbin and Kaldis, Philipp and Chen, Zijiang and Li, Wei}},
issn = {{1350-9047}},
language = {{eng}},
number = {{6}},
pages = {{1174--1188}},
publisher = {{Nature Publishing Group}},
series = {{Cell Death and Differentiation}},
title = {{Dual roles of TRF1 in tethering telomeres to the nuclear envelope and protecting them from fusion during meiosis}},
url = {{http://dx.doi.org/10.1038/s41418-017-0037-8}},
doi = {{10.1038/s41418-017-0037-8}},
volume = {{25}},
year = {{2018}},
}