TRF1 negotiates TTAGGG repeat-associated replication problems
by recruiting the BLM helicase and the TPP1/POT1 repressor of
ATR signaling

J 2014

TRF1 negotiates TTAGGG repeat-associated replication problems by recruiting the BLM helicase and the TPP1/POT1 repressor of ATR signaling

ZIMMERMANN, Michal, T. KIBE, S. KABIR and T. DE LANGE

Basic information

Original name

TRF1 negotiates TTAGGG repeat-associated replication problems by recruiting the BLM helicase and the TPP1/POT1 repressor of ATR signaling

Authors

ZIMMERMANN, Michal (203 Czech Republic, guarantor, belonging to the institution), T. KIBE (840 United States of America), S. KABIR (840 United States of America) and T. DE LANGE (840 United States of America)

Edition

GENES & DEVELOPMENT, COLD SPRING HARBOR, COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT, 2014, 0890-9369

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

Genetics and molecular biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 10.798

RIV identification code

RIV/00216224:14740/14:00074403

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1101/gad.251611.114

UT WoS

000345269300005

Keywords in English

telomere; shelterin; TRF1; BLM; replication; G quadruplex

Abstract

V originále

The semiconservative replication of telomeres is facilitated by the shelterin component TRF1. Without TRF1, replication forks stall in the telomeric repeats, leading to ATR kinase signaling upon S-phase progression, fragile metaphase telomeres that resemble the common fragile sites (CFSs), and the association of sister telomeres. In contrast, TRF1 does not contribute significantly to the end protection functions of shelterin. We addressed the mechanism of TRF1 action using mouse conditional knockouts of BLM, TRF1, TPP1, and Rap1 in combination with expression of TRF1 and TIN2 mutants. The data establish that TRF1 binds BLM to facilitate lagging but not leading strand telomeric DNA synthesis. As the template for lagging strand telomeric DNA synthesis is the TTAGGG repeat strand, TRF1-bound BLM is likely required to remove secondary structures formed by these sequences. In addition, the data establish that TRF1 deploys TIN2 and the TPP1/POT1 heterodimers in shelterin to prevent ATR during telomere replication and repress the accompanying sister telomere associations. Thus, TRF1 uses two distinct mechanisms to promote replication of telomeric DNA and circumvent the consequences of replication stress. These data are relevant to the expression of CFSs and provide insights into TIN2, which is compromised in dyskeratosis congenita (DC) and related disorders.

Links

ED1.1.00/02.0068, research and development project

Name: CEITEC - central european institute of technology

GAP205/12/0550, research and development project

Name: Dynamika vzniku shelterinového komplexu

Investor: Czech Science Foundation

Citovat

ZIMMERMANN, Michal, T. KIBE, S. KABIR and T. DE LANGE. TRF1 negotiates TTAGGG repeat-associated replication problems by recruiting the BLM helicase and the TPP1/POT1 repressor of ATR signaling. GENES & DEVELOPMENT. COLD SPRING HARBOR: COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT, 2014, vol. 28, No 22, p. 2477-2491. ISSN 0890-9369. Available from: https://dx.doi.org/10.1101/gad.251611.114.

@article{1227546,
   author = {Zimmermann, Michal and Kibe, T. and Kabir, S. and de Lange, T.},
   article_location = {COLD SPRING HARBOR},
   article_number = {22},
   doi = {http://dx.doi.org/10.1101/gad.251611.114},
   keywords = {telomere; shelterin; TRF1; BLM; replication; G quadruplex},
   language = {eng},
   issn = {0890-9369},
   journal = {GENES & DEVELOPMENT},
   title = {TRF1 negotiates TTAGGG repeat-associated replication problems by recruiting the BLM helicase and the TPP1/POT1 repressor of ATR signaling},
   url = {http://genesdev.cshlp.org/content/early/2014/10/23/gad.251611.114.full.pdf+html},
   volume = {28},
   year = {2014}
}

TY  - JOUR
ID  - 1227546
AU  - Zimmermann, Michal - Kibe, T. - Kabir, S. - de Lange, T.
PY  - 2014
TI  - TRF1 negotiates TTAGGG repeat-associated replication problems by recruiting the BLM helicase and the TPP1/POT1 repressor of ATR signaling
JF  - GENES & DEVELOPMENT
VL  - 28
IS  - 22
SP  - 2477-2491
EP  - 2477-2491
PB  - COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
SN  - 08909369
KW  - telomere
KW  - shelterin
KW  - TRF1
KW  - BLM
KW  - replication
KW  - G quadruplex
UR  - http://genesdev.cshlp.org/content/early/2014/10/23/gad.251611.114.full.pdf+html
L2  - http://genesdev.cshlp.org/content/early/2014/10/23/gad.251611.114.full.pdf+html
N2  - The semiconservative replication of telomeres is facilitated by the shelterin component TRF1. Without TRF1, replication forks stall in the telomeric repeats, leading to ATR kinase signaling upon S-phase progression, fragile metaphase telomeres that resemble the common fragile sites (CFSs), and the association of sister telomeres. In contrast, TRF1 does not contribute significantly to the end protection functions of shelterin. We addressed the mechanism of TRF1 action using mouse conditional knockouts of BLM, TRF1, TPP1, and Rap1 in combination with expression of TRF1 and TIN2 mutants. The data establish that TRF1 binds BLM to facilitate lagging but not leading strand telomeric DNA synthesis. As the template for lagging strand telomeric DNA synthesis is the TTAGGG repeat strand, TRF1-bound BLM is likely required to remove secondary structures formed by these sequences. In addition, the data establish that TRF1 deploys TIN2 and the TPP1/POT1 heterodimers in shelterin to prevent ATR during telomere replication and repress the accompanying sister telomere associations. Thus, TRF1 uses two distinct mechanisms to promote replication of telomeric DNA and circumvent the consequences of replication stress. These data are relevant to the expression of CFSs and provide insights into TIN2, which is compromised in dyskeratosis congenita (DC) and related disorders.
ER  -

ZIMMERMANN, Michal, T. KIBE, S. KABIR and T. DE LANGE. TRF1 negotiates TTAGGG repeat-associated replication problems by recruiting the BLM helicase and the TPP1/POT1 repressor of ATR signaling. \textit{GENES \&{}amp; DEVELOPMENT}. COLD SPRING HARBOR: COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT, 2014, vol.~28, No~22, p.~2477-2491. ISSN~0890-9369. Available from: https://dx.doi.org/10.1101/gad.251611.114.

Detailed Information on Publication Record