Ubiquitin-like protein UBL5 promotes the functional integrity of the Fanconi anemia pathway

Research output: Contribution to journal › Journal article › Research › peer-review

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Ubiquitin-like protein UBL5 promotes the functional integrity of the Fanconi anemia pathway. / Oka, Yasuyoshi; Bekker-Jensen, Simon; Mailand, Niels.

In: E M B O Journal, Vol. 34, 09.04.2015, p. 1385-1398.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Oka, Y, Bekker-Jensen, S & Mailand, N 2015, 'Ubiquitin-like protein UBL5 promotes the functional integrity of the Fanconi anemia pathway', E M B O Journal, vol. 34, pp. 1385-1398. https://doi.org/10.15252/embj.201490376

APA

Oka, Y., Bekker-Jensen, S., & Mailand, N. (2015). Ubiquitin-like protein UBL5 promotes the functional integrity of the Fanconi anemia pathway. E M B O Journal, 34, 1385-1398. https://doi.org/10.15252/embj.201490376

Vancouver

Oka Y, Bekker-Jensen S, Mailand N. Ubiquitin-like protein UBL5 promotes the functional integrity of the Fanconi anemia pathway. E M B O Journal. 2015 Apr 9;34:1385-1398. https://doi.org/10.15252/embj.201490376

Author

Oka, Yasuyoshi ; Bekker-Jensen, Simon ; Mailand, Niels. / Ubiquitin-like protein UBL5 promotes the functional integrity of the Fanconi anemia pathway. In: E M B O Journal. 2015 ; Vol. 34. pp. 1385-1398.

Bibtex

@article{92c5c3a1494b4dcead10c7fdd8a4fd87,
title = "Ubiquitin-like protein UBL5 promotes the functional integrity of the Fanconi anemia pathway",
abstract = "Ubiquitin and ubiquitin-like proteins (UBLs) function in a wide array of cellular processes. UBL5 is an atypical UBL that does not form covalent conjugates with cellular proteins and which has a known role in modulating pre-mRNA splicing. Here, we report an unexpected involvement of human UBL5 in promoting the function of the Fanconi anemia (FA) pathway for repair of DNA interstrand crosslinks (ICLs), mediated by a specific interaction with the central FA pathway component FANCI. UBL5-deficient cells display spliceosome-independent reduction of FANCI protein stability, defective FANCI function in response to DNA damage and hypersensitivity to ICLs. By mapping the sequence determinants underlying UBL5-FANCI binding, we generated separation-of-function mutants to demonstrate that key aspects of FA pathway function, including FANCI-FANCD2 heterodimerization, FANCD2 and FANCI monoubiquitylation and maintenance of chromosome stability after ICLs, are compromised when the UBL5-FANCI interaction is selectively inhibited by mutations in either protein. Together, our findings establish UBL5 as a factor that promotes the functionality of the FA DNA repair pathway.",
author = "Yasuyoshi Oka and Simon Bekker-Jensen and Niels Mailand",
note = "{\textcopyright} 2015 The Authors.",
year = "2015",
month = apr,
day = "9",
doi = "10.15252/embj.201490376",
language = "English",
volume = "34",
pages = "1385--1398",
journal = "E M B O Journal",
issn = "0261-4189",
publisher = "Wiley-Blackwell",

}

RIS

TY - JOUR

T1 - Ubiquitin-like protein UBL5 promotes the functional integrity of the Fanconi anemia pathway

AU - Oka, Yasuyoshi

AU - Bekker-Jensen, Simon

AU - Mailand, Niels

N1 - © 2015 The Authors.

PY - 2015/4/9

Y1 - 2015/4/9

N2 - Ubiquitin and ubiquitin-like proteins (UBLs) function in a wide array of cellular processes. UBL5 is an atypical UBL that does not form covalent conjugates with cellular proteins and which has a known role in modulating pre-mRNA splicing. Here, we report an unexpected involvement of human UBL5 in promoting the function of the Fanconi anemia (FA) pathway for repair of DNA interstrand crosslinks (ICLs), mediated by a specific interaction with the central FA pathway component FANCI. UBL5-deficient cells display spliceosome-independent reduction of FANCI protein stability, defective FANCI function in response to DNA damage and hypersensitivity to ICLs. By mapping the sequence determinants underlying UBL5-FANCI binding, we generated separation-of-function mutants to demonstrate that key aspects of FA pathway function, including FANCI-FANCD2 heterodimerization, FANCD2 and FANCI monoubiquitylation and maintenance of chromosome stability after ICLs, are compromised when the UBL5-FANCI interaction is selectively inhibited by mutations in either protein. Together, our findings establish UBL5 as a factor that promotes the functionality of the FA DNA repair pathway.

AB - Ubiquitin and ubiquitin-like proteins (UBLs) function in a wide array of cellular processes. UBL5 is an atypical UBL that does not form covalent conjugates with cellular proteins and which has a known role in modulating pre-mRNA splicing. Here, we report an unexpected involvement of human UBL5 in promoting the function of the Fanconi anemia (FA) pathway for repair of DNA interstrand crosslinks (ICLs), mediated by a specific interaction with the central FA pathway component FANCI. UBL5-deficient cells display spliceosome-independent reduction of FANCI protein stability, defective FANCI function in response to DNA damage and hypersensitivity to ICLs. By mapping the sequence determinants underlying UBL5-FANCI binding, we generated separation-of-function mutants to demonstrate that key aspects of FA pathway function, including FANCI-FANCD2 heterodimerization, FANCD2 and FANCI monoubiquitylation and maintenance of chromosome stability after ICLs, are compromised when the UBL5-FANCI interaction is selectively inhibited by mutations in either protein. Together, our findings establish UBL5 as a factor that promotes the functionality of the FA DNA repair pathway.

U2 - 10.15252/embj.201490376

DO - 10.15252/embj.201490376

M3 - Journal article

C2 - 25862789

VL - 34

SP - 1385

EP - 1398

JO - E M B O Journal

JF - E M B O Journal

SN - 0261-4189

ER -

ID: 139975244