Transcription-associated recombination is independent of XRCC2 and mechanistically separate from homology-directed DNA double-strand break repair

It has previously been shown that transcription greatly enhances recombination in mammalian cells. However, the proteins involved in catalysing this process and the recombination pathways involved in transcription-associated recombination (TAR) are still unknown. It is well established that both the...

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Main Authors: Savolainen, L, Helleday, T
Format: Journal article
Language:English
Published: Oxford University Press 2009
Subjects:
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author Savolainen, L
Helleday, T
author_facet Savolainen, L
Helleday, T
author_sort Savolainen, L
collection OXFORD
description It has previously been shown that transcription greatly enhances recombination in mammalian cells. However, the proteins involved in catalysing this process and the recombination pathways involved in transcription-associated recombination (TAR) are still unknown. It is well established that both the BRCA2 protein and the RAD51 paralog protein XRCC2 are required for homologous recombination. Here, we show that the BRCA2 protein is also required for TAR, while the XRCC2 protein is not involved. Expression of the XRCC2 gene in XRCC2 mutated irs1 cells restores the defect in homologous recombination repair of an I-SceI-induced DNA double-strand break, while TAR is unaffected. Interestingly, the XRCC2-deficient irs1 cells are also proficient in recombination induced at slowed replication forks, suggesting that TAR is mechanistically linked with this recombination pathway. In conclusion, we show that TAR depends on BRCA2 but is independent of XRCC2, and that this recombination pathway is separate from that used to repair a two-ended DNA double-strand break.
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spelling oxford-uuid:40f3018a-02c1-476a-83ae-345b7b97a2cd2022-03-26T14:40:48ZTranscription-associated recombination is independent of XRCC2 and mechanistically separate from homology-directed DNA double-strand break repairJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:40f3018a-02c1-476a-83ae-345b7b97a2cdLife SciencesEnglishOxford University Research Archive - ValetOxford University Press2009Savolainen, LHelleday, TIt has previously been shown that transcription greatly enhances recombination in mammalian cells. However, the proteins involved in catalysing this process and the recombination pathways involved in transcription-associated recombination (TAR) are still unknown. It is well established that both the BRCA2 protein and the RAD51 paralog protein XRCC2 are required for homologous recombination. Here, we show that the BRCA2 protein is also required for TAR, while the XRCC2 protein is not involved. Expression of the XRCC2 gene in XRCC2 mutated irs1 cells restores the defect in homologous recombination repair of an I-SceI-induced DNA double-strand break, while TAR is unaffected. Interestingly, the XRCC2-deficient irs1 cells are also proficient in recombination induced at slowed replication forks, suggesting that TAR is mechanistically linked with this recombination pathway. In conclusion, we show that TAR depends on BRCA2 but is independent of XRCC2, and that this recombination pathway is separate from that used to repair a two-ended DNA double-strand break.
spellingShingle Life Sciences
Savolainen, L
Helleday, T
Transcription-associated recombination is independent of XRCC2 and mechanistically separate from homology-directed DNA double-strand break repair
title Transcription-associated recombination is independent of XRCC2 and mechanistically separate from homology-directed DNA double-strand break repair
title_full Transcription-associated recombination is independent of XRCC2 and mechanistically separate from homology-directed DNA double-strand break repair
title_fullStr Transcription-associated recombination is independent of XRCC2 and mechanistically separate from homology-directed DNA double-strand break repair
title_full_unstemmed Transcription-associated recombination is independent of XRCC2 and mechanistically separate from homology-directed DNA double-strand break repair
title_short Transcription-associated recombination is independent of XRCC2 and mechanistically separate from homology-directed DNA double-strand break repair
title_sort transcription associated recombination is independent of xrcc2 and mechanistically separate from homology directed dna double strand break repair
topic Life Sciences
work_keys_str_mv AT savolainenl transcriptionassociatedrecombinationisindependentofxrcc2andmechanisticallyseparatefromhomologydirecteddnadoublestrandbreakrepair
AT helledayt transcriptionassociatedrecombinationisindependentofxrcc2andmechanisticallyseparatefromhomologydirecteddnadoublestrandbreakrepair