Molecular basis of chromatin remodeling by Rhp26, a yeast CSB ortholog

Wang, Wei; Xu, Jun; Limbo, Oliver; Fei, Jia; Kassavetis, George A.; Chong, Jenny; Kadonaga, James T.; Russell, Paul; Li, Bing; Wang, Dong

doi:10.1073/pnas.1818163116

Cited by 11 publications

(7 citation statements)

References 56 publications

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“…Alternatively, H3K36 methylation may also regulate Rad26 activity, since it has been reported that histone H3 and H4 tails are important for the activity of Rhp26 ( S . pombe Rad26 homolog) in nucleosomes [ 64 ]. Future studies will be required to explore these possible mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Set2 histone methyltransferase regulates transcription coupled-nucleotide excision repair in yeast

et al. 2022

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Helix-distorting DNA lesions, including ultraviolet (UV) light-induced damage, are repaired by the global genomic-nucleotide excision repair (GG-NER) and transcription coupled-nucleotide excision repair (TC-NER) pathways. Previous studies have shown that histone post-translational modifications (PTMs) such as histone acetylation and methylation can promote GG-NER in chromatin. Whether histone PTMs also regulate the repair of DNA lesions by the TC-NER pathway in transcribed DNA is unknown. Here, we report that histone H3 K36 methylation (H3K36me) by the Set2 histone methyltransferase in yeast regulates TC-NER. Mutations in Set2 or H3K36 result in UV sensitivity that is epistatic with Rad26, the primary TC-NER factor in yeast, and cause a defect in the repair of UV damage across the yeast genome. We further show that mutations in Set2 or H3K36 in a GG-NER deficient strain (i.e., rad16Δ) partially rescue its UV sensitivity. Our data indicate that deletion of SET2 rescues UV sensitivity in a GG-NER deficient strain by activating cryptic antisense transcription, so that the non-transcribed strand (NTS) of yeast genes is repaired by TC-NER. These findings indicate that Set2 methylation of H3K36 establishes transcriptional asymmetry in repair by promoting canonical TC-NER of the transcribed strand (TS) and suppressing cryptic TC-NER of the NTS.

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Section: Discussionmentioning

confidence: 99%

Set2 histone methyltransferase regulates transcription coupled-nucleotide excision repair in yeast

et al. 2022

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“…In the structure, the extended gating helix, which would be incompatible with duplex DNA, appears like a rudder just ahead of where the two DNA strands reanneal. In addition to assisting Pol II, CSB/Rad26 can reposition nucleosomes (22,24,130), raising the possibility that translocation on DNA with an extended gating helix may also occur on the nucleosome.…”

Section: The Gating Helix Is a Remodeler-specific Element Poised To C...mentioning

confidence: 99%

Biophysics of Chromatin Remodeling

Nodelman

Bowman

2021

Annu. Rev. Biophys.

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As primary carriers of epigenetic information and gatekeepers of genomic DNA, nucleosomes are essential for proper growth and development of all eukaryotic cells. Although they are intrinsically dynamic, nucleosomes are actively reorganized by ATP-dependent chromatin remodelers. Chromatin remodelers contain helicase-like ATPase motor domains that can translocate along DNA, and a long-standing question in the field is how this activity is used to reposition or slide nucleosomes. In addition to ratcheting along DNA like their helicase ancestors, remodeler ATPases appear to dictate specific alternating geometries of the DNA duplex, providing an unexpected means for moving DNA past the histone core. Emerging evidence supports twist-based mechanisms for ATP-driven repositioning of nucleosomes along DNA. In this review, we discuss core experimental findings and ideas that have shaped the view of how nucleosome sliding may be achieved. Expected final online publication date for the Annual Review of Biophysics, Volume 50 is May 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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“…2b and 3d ; Supplementary Movie 1 ). Indeed, we previously identified a CSB-specific coupling motif in the CTD (residues 900–910 in Rhp26 and 904–914 in Rad26) that couples the ATPase and chromatin remodeling/translocation activities 37 . The interactions between the newly modeled CTD and HD2-1 linker may explain how this region couples the ATPase and chromatin remodeling/translocation activities.…”

Section: Resultsmentioning

confidence: 99%

Mechanism of Rad26-assisted rescue of stalled RNA polymerase II in transcription-coupled repair

Cheng

Dodd

et al. 2021

Nat Commun

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Transcription-coupled repair is essential for the removal of DNA lesions from the transcribed genome. The pathway is initiated by CSB protein binding to stalled RNA polymerase II. Mutations impairing CSB function cause severe genetic disease. Yet, the ATP-dependent mechanism by which CSB powers RNA polymerase to bypass certain lesions while triggering excision of others is incompletely understood. Here we build structural models of RNA polymerase II bound to the yeast CSB ortholog Rad26 in nucleotide-free and bound states. This enables simulations and graph-theoretical analyses to define partitioning of this complex into dynamic communities and delineate how its structural elements function together to remodel DNA. We identify an allosteric pathway coupling motions of the Rad26 ATPase modules to changes in RNA polymerase and DNA to unveil a structural mechanism for CSB-assisted progression past less bulky lesions. Our models allow functional interpretation of the effects of Cockayne syndrome disease mutations.

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Molecular basis of chromatin remodeling by Rhp26, a yeast CSB ortholog

Cited by 11 publications

References 56 publications

Set2 histone methyltransferase regulates transcription coupled-nucleotide excision repair in yeast

Set2 histone methyltransferase regulates transcription coupled-nucleotide excision repair in yeast

Biophysics of Chromatin Remodeling

Mechanism of Rad26-assisted rescue of stalled RNA polymerase II in transcription-coupled repair

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