Universität zu Köln

Goulielmaki, Evi, Tsekrekou, Maria ORCID: 0000-0002-0635-1499, Batsiotos, Nikos, Ascensao-Ferreira, Mariana, Ledaki, Eleftheria, Stratigi, Kalliopi, Chatzinikolaou, Georgia, Topalis, Pantelis ORCID: 0000-0002-1635-4810, Kosteas, Theodore, Altmuller, Janine, Demmers, Jeroen A., Barbosa-Morais, Nuno L. and Garinis, George A. (2021). The splicing factor XAB2 interacts with ERCC1-XPF and XPG for R-loop processing. Nat. Commun., 12 (1). BERLIN: NATURE RESEARCH. ISSN 2041-1723

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Abstract

RNA splicing, transcription and the DNA damage response are intriguingly linked in mammals but the underlying mechanisms remain poorly understood. Using an in vivo biotinylation tagging approach in mice, we show that the splicing factor XAB2 interacts with the core spliceosome and that it binds to spliceosomal U4 and U6 snRNAs and pre-mRNAs in developing livers. XAB2 depletion leads to aberrant intron retention, R-loop formation and DNA damage in cells. Studies in illudin S-treated cells and Csb(m/m) developing livers reveal that transcription-blocking DNA lesions trigger the release of XAB2 from all RNA targets tested. Immunoprecipitation studies reveal that XAB2 interacts with ERCC1-XPF and XPG endonucleases outside nucleotide excision repair and that the trimeric protein complex binds RNA:DNA hybrids under conditions that favor the formation of R-loops. Thus, XAB2 functionally links the spliceosomal response to DNA damage with R-loop processing with important ramifications for transcription-coupled DNA repair disorders. XPA-binding protein (XAB)-2 is the human homologue of the yeast pre-mRNA splicing factor Syf1. Here the authors use an in vivo biotinylation tagging approach to show XAB2's role in DNA repair, RNA splicing and transcription during mammalian development.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Goulielmaki, Evi UNSPECIFIED UNSPECIFIED UNSPECIFIED Tsekrekou, Maria UNSPECIFIED orcid.org/0000-0002-0635-1499 UNSPECIFIED Batsiotos, Nikos UNSPECIFIED UNSPECIFIED UNSPECIFIED Ascensao-Ferreira, Mariana UNSPECIFIED UNSPECIFIED UNSPECIFIED Ledaki, Eleftheria UNSPECIFIED UNSPECIFIED UNSPECIFIED Stratigi, Kalliopi UNSPECIFIED UNSPECIFIED UNSPECIFIED Chatzinikolaou, Georgia UNSPECIFIED UNSPECIFIED UNSPECIFIED Topalis, Pantelis UNSPECIFIED orcid.org/0000-0002-1635-4810 UNSPECIFIED Kosteas, Theodore UNSPECIFIED UNSPECIFIED UNSPECIFIED Altmuller, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED Demmers, Jeroen A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Barbosa-Morais, Nuno L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Garinis, George A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-594173
DOI:	10.1038/s41467-021-23505-1
Journal or Publication Title:	Nat. Commun.
Volume:	12
Number:	1
Date:	2021
Publisher:	NATURE RESEARCH
Place of Publication:	BERLIN
ISSN:	2041-1723
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NUCLEOTIDE EXCISION-REPAIR; COUPLED DNA-REPAIR; PRP19 COMPLEX; RNA; TRANSCRIPTION; DAMAGE; PROTEIN; TARGET; SPLICEOSOME; CANCER Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59417