The Fanconi anaemia components UBE2T and FANCM are functionally linked to nucleotide excision repair.

The many proteins that function in the Fanconi anaemia (FA) monoubiquitylation pathway initiate replicative DNA crosslink repair. However, it is not clear whether individual FA genes participate in DNA repair pathways other than homologous recombination and translesion bypass. Here we show that avia...

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Main Authors: Ian R Kelsall, Judith Langenick, Craig MacKay, Ketan J Patel, Arno F Alpi
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0036970&type=printable
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author Ian R Kelsall
Judith Langenick
Craig MacKay
Ketan J Patel
Arno F Alpi
author_facet Ian R Kelsall
Judith Langenick
Craig MacKay
Ketan J Patel
Arno F Alpi
author_sort Ian R Kelsall
collection DOAJ
description The many proteins that function in the Fanconi anaemia (FA) monoubiquitylation pathway initiate replicative DNA crosslink repair. However, it is not clear whether individual FA genes participate in DNA repair pathways other than homologous recombination and translesion bypass. Here we show that avian DT40 cell knockouts of two integral FA genes--UBE2T and FANCM are unexpectedly sensitive to UV-induced DNA damage. Comprehensive genetic dissection experiments indicate that both of these FA genes collaborate to promote nucleotide excision repair rather than translesion bypass to protect cells form UV genotoxicity. Furthermore, UBE2T deficiency impacts on the efficient removal of the UV-induced photolesion cyclobutane pyrimidine dimer. Therefore, this work reveals that the FA pathway shares two components with nucleotide excision repair, intimating not only crosstalk between the two major repair pathways, but also potentially identifying a UBE2T-mediated ubiquitin-signalling response pathway that contributes to nucleotide excision repair.
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spelling doaj-art-591308a5da0d441b86b6059e5a89f4092025-08-20T03:09:48ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0175e3697010.1371/journal.pone.0036970The Fanconi anaemia components UBE2T and FANCM are functionally linked to nucleotide excision repair.Ian R KelsallJudith LangenickCraig MacKayKetan J PatelArno F AlpiThe many proteins that function in the Fanconi anaemia (FA) monoubiquitylation pathway initiate replicative DNA crosslink repair. However, it is not clear whether individual FA genes participate in DNA repair pathways other than homologous recombination and translesion bypass. Here we show that avian DT40 cell knockouts of two integral FA genes--UBE2T and FANCM are unexpectedly sensitive to UV-induced DNA damage. Comprehensive genetic dissection experiments indicate that both of these FA genes collaborate to promote nucleotide excision repair rather than translesion bypass to protect cells form UV genotoxicity. Furthermore, UBE2T deficiency impacts on the efficient removal of the UV-induced photolesion cyclobutane pyrimidine dimer. Therefore, this work reveals that the FA pathway shares two components with nucleotide excision repair, intimating not only crosstalk between the two major repair pathways, but also potentially identifying a UBE2T-mediated ubiquitin-signalling response pathway that contributes to nucleotide excision repair.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0036970&type=printable
spellingShingle Ian R Kelsall
Judith Langenick
Craig MacKay
Ketan J Patel
Arno F Alpi
The Fanconi anaemia components UBE2T and FANCM are functionally linked to nucleotide excision repair.
PLoS ONE
title The Fanconi anaemia components UBE2T and FANCM are functionally linked to nucleotide excision repair.
title_full The Fanconi anaemia components UBE2T and FANCM are functionally linked to nucleotide excision repair.
title_fullStr The Fanconi anaemia components UBE2T and FANCM are functionally linked to nucleotide excision repair.
title_full_unstemmed The Fanconi anaemia components UBE2T and FANCM are functionally linked to nucleotide excision repair.
title_short The Fanconi anaemia components UBE2T and FANCM are functionally linked to nucleotide excision repair.
title_sort fanconi anaemia components ube2t and fancm are functionally linked to nucleotide excision repair
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0036970&type=printable
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