2014
Human ISWI complexes are targeted by SMARCA5 ATPase and SLIDE domains to help resolve lesion-stalled transcription
Publication
Publication
Nucleic Acids Research , Volume 42 - Issue 13 p. 8473- 8485
Chromatin compaction of deoxyribonucleic acid (DNA) presents a major challenge to the detection and removal of DNA damage. Helix-distorting DNA lesions that block transcription are specifically repaired by transcription-coupled nucleotide excision repair, which is initiated by binding of the CSB protein to lesion-stalled RNA polymerase II. Using live cell imaging, we identify a novel function for two distinct mammalian ISWI adenosine triphosphate (ATP)-dependent chromatin remodeling complexes in resolving lesion-stalled transcription. Human ISWI isoform SMARCA5/SNF2H and its binding partners ACF1 and WSTF are rapidly recruited to UV-C induced DNA damage to specifically facilitate CSB binding and to promote transcription recovery. SMARCA5 targeting to UV-C damage depends on transcription and histone modifications and requires functional SWI2/SNF2-ATPase and SLIDE domains. After initial recruitment to UV damage, SMARCA5 re-localizes away from the center of DNA damage, requiring its HAND domain. Our studies support a model in which SMARCA5 targeting to DNA damage-stalled transcription sites is controlled by an ATP-hydrolysis-dependent scanning and proofreading mechanism, highlighting how SWI2/SNF2 chromatin remodelers identify and bind nucleosomes containing damaged DNA.
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doi.org/10.1093/nar/gku565, hdl.handle.net/1765/55931 | |
Nucleic Acids Research | |
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Organisation | Biophysical Genomics, Department Cell Biology & Genetics |
Aydin, Ö., Marteijn, J., Ribeiro-Silva, C., Rodríguez López, A., Wijgers, N., Smeenk, G., … Lans, H. (2014). Human ISWI complexes are targeted by SMARCA5 ATPase and SLIDE domains to help resolve lesion-stalled transcription. Nucleic Acids Research, 42(13), 8473–8485. doi:10.1093/nar/gku565 |
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nar-00549-m-2014-File010.pdf supplementary file 1 , 1mb | |
nar-00549-m-2014-File011.avi supplementary file 2 , 3mb | |
nar-00549-m-2014-File012.avi Supplementary file 3 , 5mb | |
pubmedcentral Author Manuscript |