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Alexandra Lusser - One of the best experts on this subject based on the ideXlab platform.
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Embryonic stem cell differentiation requires full length CHD1
Scientific Reports, 2015Co-Authors: Paolo Piatti, Andreas Villunger, Stephan Geley, Yan Ting Shue, Claudia Soratroi, Markus Moser, Alexandra LusserAbstract:The modulation of chromatin dynamics by ATP-dependent chromatin remodeling factors has been recognized as an important mechanism to regulate the balancing of self-renewal and pluripotency in embryonic stem cells (ESCs). Here we have studied the effects of a partial deletion of the gene encoding the chromatin remodeling factor CHD1 that generates an N-terminally truncated version of CHD1 in mouse ESCs in vitro as well as in vivo . We found that a previously uncharacterized serine-rich region (SRR) at the N-terminus is not required for chromatin assembly activity of CHD1 but that it is subject to phosphorylation. Expression of CHD1 lacking this region in ESCs resulted in aberrant differentiation properties of these cells. The self-renewal capacity and ESC chromatin structure, however, were not affected. Notably, we found that newly established ESCs derived from CHD1 ^ Δ2/Δ2 mutant mice exhibited similar differentiation defects as in vitro generated mutant ESCs, even though the N-terminal truncation of CHD1 was fully compatible with embryogenesis and post-natal life in the mouse. These results underscore the importance of CHD1 for the regulation of pluripotency in ESCs and provide evidence for a hitherto unrecognized critical role of the phosphorylated N-terminal SRR for full functionality of CHD1.
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The chromodomains of CHD1 are critical for enzymatic activity but less important for chromatin localization
Nucleic acids research, 2010Co-Authors: Stefano Morettini, Martin Tribus, Anette Zeilner, Johanna Sebald, Beatriz Campo-fernandez, Gabriele Scheran, Hildegard Wörle, Valerie Podhraski, Dmitry V. Fyodorov, Alexandra LusserAbstract:The molecular motor protein CHD1 has been implicated in the regulation of transcription and in the transcription-independent genome-wide incorporation of H3.3 into paternal chromatin in Drosophila melanogaster. A key feature of CHD1 is the presence of two chromodomains, which can bind to histone H3 methylated at lysine 4 and thus might serve to recruit and/or maintain CHD1 at the chromatin. Here, we describe genetic and biochemical approaches to the study of the Drosophila CHD1 chromodomains. We found that overall localization of CHD1 on polytene chromosomes does not appreciably change in chromodomain-mutant flies. In contrast, the chromodomains are important for transcription-independent activities of CHD1 during early embryonic development as well as for transcriptional regulation of several heat shock genes. However, neither CHD1 nor its chromodomains are needed for RNA polymerase II localization and H3K4 methylation but loss of CHD1 decreases transcription-induced histone eviction at the Hsp70 gene in vivo. Chromodomain mutations negatively affect the chromatin assembly activities of CHD1 in vitro, and they appear to be involved in linking the ATP-dependent motor to the chromatin assembly function of CHD1.
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CenH3/CID incorporation is not dependent on the chromatin assembly factor CHD1 in Drosophila
PloS one, 2010Co-Authors: Valerie Podhraski, Beatriz Campo-fernandez, Hildegard Wörle, Dmitry V. Fyodorov, Paolo Piatti, Harald Niederegger, Günther Böck, Alexandra LusserAbstract:CHD1 is a SNF2-related ATPase that is required for the genome-wide incorporation of variant histone H3.3 in the paternal pronucleus as well as in transcriptionally active nuclei in Drosophila embryos. The S. pombe and vertebrate orthologs of CHD1 have been implicated in the assembly of the centromeric histone H3 variant CenH3CENP-A, which occurs in a DNA replication-independent manner. Here, we examined whether CHD1 participates in the assembly of CenH3CID in Drosophila. In contrast to the findings in fission yeast and vertebrate cells, our evidence clearly argues against such a role for CHD1 in Drosophila. CHD1 does not localize to centromeres in either S2 cells or developing fly embryos. Down-regulation of CHD1 in S2 cells by RNAi reveals unchanged levels of CenH3CID at the centromeres. Most notably, ablation of functional CHD1 in CHD1 mutant fly embryos does not interfere with centromere and kinetochore assembly, as the levels and localization of CenH3CID, CENP-C and BubR1 in the mutant embryos remain similar to those seen in wild-type embryos. These results indicate that Drosophila CHD1 has no direct function in the incorporation of the centromeric H3 variant CenH3CID into chromatin. Therefore, centromeric chromatin assembly may involve different mechanisms in different organisms.
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cenh3 cid incorporation is not dependent on the chromatin assembly factor CHD1 in drosophila
PLOS ONE, 2010Co-Authors: Valerie Podhraski, Hildegard Wörle, Dmitry V. Fyodorov, Paolo Piatti, Harald Niederegger, Günther Böck, Beatriz Campofernandez, Alexandra LusserAbstract:CHD1 is a SNF2-related ATPase that is required for the genome-wide incorporation of variant histone H3.3 in the paternal pronucleus as well as in transcriptionally active nuclei in Drosophila embryos. The S. pombe and vertebrate orthologs of CHD1 have been implicated in the assembly of the centromeric histone H3 variant CenH3CENP-A, which occurs in a DNA replication-independent manner. Here, we examined whether CHD1 participates in the assembly of CenH3CID in Drosophila. In contrast to the findings in fission yeast and vertebrate cells, our evidence clearly argues against such a role for CHD1 in Drosophila. CHD1 does not localize to centromeres in either S2 cells or developing fly embryos. Down-regulation of CHD1 in S2 cells by RNAi reveals unchanged levels of CenH3CID at the centromeres. Most notably, ablation of functional CHD1 in CHD1 mutant fly embryos does not interfere with centromere and kinetochore assembly, as the levels and localization of CenH3CID, CENP-C and BubR1 in the mutant embryos remain similar to those seen in wild-type embryos. These results indicate that Drosophila CHD1 has no direct function in the incorporation of the centromeric H3 variant CenH3CID into chromatin. Therefore, centromeric chromatin assembly may involve different mechanisms in different organisms.
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Distinct activities of CHD1 and ACF in ATP-dependent chromatin assembly.
Nature structural & molecular biology, 2005Co-Authors: Alexandra Lusser, Debra L. Urwin, James T. KadonagaAbstract:CHD1 is a chromodomain-containing protein in the SNF2-like family of ATPases. Here we show that CHD1 exists predominantly as a monomer and functions as an ATP-utilizing chromatin assembly factor. This reaction involves purified CHD1, NAP1 chaperone, core histones and relaxed DNA. CHD1 catalyzes the ATP-dependent transfer of histones from the NAP1 chaperone to the DNA by a processive mechanism that yields regularly spaced nucleosomes. The comparative analysis of CHD1 and ACF revealed that CHD1 assembles chromatin with a shorter nucleosome repeat length than ACF. In addition, ACF, but not CHD1, can assemble chromatin containing histone H1, which is involved in the formation of higher-order chromatin structure and transcriptional repression. These results suggest a role for CHD1 in the assembly of active chromatin and a function of ACF in the assembly of repressive chromatin.
Vishwanath R Iyer - One of the best experts on this subject based on the ideXlab platform.
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the atp dependent chromatin remodeler CHD1 is recruited by transcription elongation factors and maintains h3k4me3 h3k36me3 domains at actively transcribed and spliced genes
Nucleic Acids Research, 2017Co-Authors: Yaelim Lee, Daechan Park, Vishwanath R IyerAbstract:CHD1 (Chromodomain Helicase DNA Binding Protein 1) is a conserved ATP-dependent chromatin remodeler that maintains the nucleosomal structure of chromatin, but the determinants of its specificity and its impact on gene expression are not well defined. To identify the determinants of CHD1 binding specificity in the yeast genome, we investigated CHD1 occupancy in mutants of several candidate factors. We found that several components of the PAF1 transcription elongation complex contribute to CHD1 recruitment to highly transcribed genes and identified Spt4 as a factor that appears to negatively modulate CHD1 binding to chromatin. We discovered that CHD1 loss alters H3K4me3 and H3K36me3 patterns throughout the yeast genome. Interestingly, the aberrant histone H3 methylation patterns were predominantly observed within 1 kb from the transcription start site, where both histone H3 methylation marks co-occur. A reciprocal change between the two marks was obvious in the absence of CHD1, suggesting a role for CHD1 in establishing or maintaining the boundaries of these largely mutually exclusive histone marks. Strikingly, intron-containing genes were most susceptible to CHD1 loss and exhibited a high degree of histone H3 methylation changes. Intron retention was significantly lower in the absence of CHD1, suggesting that CHD1 function as a chromatin remodeler could indirectly affect RNA splicing.
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The ATP-dependent chromatin remodeler CHD1 is recruited by transcription elongation factors and maintains H3K4me3/H3K36me3 domains at actively transcribed and spliced genes.
Nucleic acids research, 2017Co-Authors: Yaelim Lee, Daechan Park, Vishwanath R IyerAbstract:CHD1 (Chromodomain Helicase DNA Binding Protein 1) is a conserved ATP-dependent chromatin remodeler that maintains the nucleosomal structure of chromatin, but the determinants of its specificity and its impact on gene expression are not well defined. To identify the determinants of CHD1 binding specificity in the yeast genome, we investigated CHD1 occupancy in mutants of several candidate factors. We found that several components of the PAF1 transcription elongation complex contribute to CHD1 recruitment to highly transcribed genes and identified Spt4 as a factor that appears to negatively modulate CHD1 binding to chromatin. We discovered that CHD1 loss alters H3K4me3 and H3K36me3 patterns throughout the yeast genome. Interestingly, the aberrant histone H3 methylation patterns were predominantly observed within 1 kb from the transcription start site, where both histone H3 methylation marks co-occur. A reciprocal change between the two marks was obvious in the absence of CHD1, suggesting a role for CHD1 in establishing or maintaining the boundaries of these largely mutually exclusive histone marks. Strikingly, intron-containing genes were most susceptible to CHD1 loss and exhibited a high degree of histone H3 methylation changes. Intron retention was significantly lower in the absence of CHD1, suggesting that CHD1 function as a chromatin remodeler could indirectly affect RNA splicing.
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CHD1 co-localizes with early transcription elongation factors independently of H3K36 methylation and releases stalled RNA polymerase II at introns
Epigenetics & Chromatin, 2014Co-Authors: Daechan Park, Haridha Shivram, Vishwanath R IyerAbstract:Background Chromatin consists of ordered nucleosomal arrays that are controlled by highly conserved adenosine triphosphate (ATP)-dependent chromatin remodeling complexes. One such remodeler, chromodomain helicase DNA binding protein 1 (CHD1), is believed to play an integral role in nucleosomal organization, as the loss of CHD1 is known to disrupt chromatin. However, the specificity and basis for the functional and physical localization of CHD1 on chromatin remains largely unknown. Results Using genome-wide approaches, we found that the loss of CHD1 significantly disrupted nucleosome arrays within the gene bodies of highly transcribed genes. We also found that CHD1 is physically recruited to gene bodies, and that its occupancy specifically corresponds to that of the early elongating form of RNA polymerase, RNAPII Ser 5-P. Conversely, RNAPII Ser 5-P occupancy was affected by the loss of CHD1, suggesting that CHD1 is associated with early transcription elongation. Surprisingly, the occupancy of RNAPII Ser 5-P was affected by the loss of CHD1 specifically at intron-containing genes. Nucleosome turnover was also affected at these sites in the absence of CHD1. We also found that deletion of the histone methyltransferase for H3K36 ( SET2 ) did not affect either CHD1 occupancy or nucleosome organization genome-wide. Conclusions CHD1 is specifically recruited onto the gene bodies of highly transcribed genes in an elongation-dependent but H3K36me3-independent manner. CHD1 co-localizes with the early elongating form of RNA polymerase, and affects the occupancy of RNAPII only at genes containing introns, suggesting a role in relieving splicing-related pausing of RNAPII.
Hanspeter Naegeli - One of the best experts on this subject based on the ideXlab platform.
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Chromatin remodeler CHD1 promotes XPC‐to‐TFIIH handover of nucleosomal UV lesions in nucleotide excision repair
The EMBO journal, 2017Co-Authors: Peter Rüthemann, Chiara Balbo Pogliano, Tamara Codilupi, Zuzana Garajova, Hanspeter NaegeliAbstract:Ultraviolet (UV) light induces mutagenic cyclobutane pyrimidine dimers (CPDs) in nucleosomal DNA that is tightly wrapped around histone octamers. How global-genome nucleotide excision repair (GG-NER) processes CPDs despite that this chromatin arrangement is poorly understood. An increased chromatin association of CHD1 (chromodomain helicase DNA-binding 1) upon UV irradiation indicated possible roles of this chromatin remodeler in the UV damage response. Immunoprecipitation of chromatin fragments revealed that CHD1 co-localizes in part with GG-NER factors. Chromatin fractionation showed that the UV-dependent recruitment of CHD1 occurs to UV lesions in histone-assembled nucleosomal DNA and that this CHD1 relocation requires the lesion sensor XPC (xeroderma pigmentosum group C). In situ immunofluorescence analyses further demonstrate that CHD1 facilitates substrate handover from XPC to the downstream TFIIH (transcription factor IIH). Consequently, CHD1 depletion slows down CPD excision and sensitizes cells to UV-induced cytotoxicity. The finding of a CHD1-driven lesion handover between sequentially acting GG-NER factors on nucleosomal histone octamers suggests that chromatin provides a recognition scaffold enabling the detection of a subset of CPDs.
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chromatin remodeler CHD1 promotes xpc to tfiih handover of nucleosomal uv lesions in nucleotide excision repair
The EMBO Journal, 2017Co-Authors: Peter Rüthemann, Chiara Balbo Pogliano, Tamara Codilupi, Zuzana Garajova, Hanspeter NaegeliAbstract:Ultraviolet (UV) light induces mutagenic cyclobutane pyrimidine dimers (CPDs) in nucleosomal DNA that is tightly wrapped around histone octamers. How global-genome nucleotide excision repair (GG-NER) processes CPDs despite that this chromatin arrangement is poorly understood. An increased chromatin association of CHD1 (chromodomain helicase DNA-binding 1) upon UV irradiation indicated possible roles of this chromatin remodeler in the UV damage response. Immunoprecipitation of chromatin fragments revealed that CHD1 co-localizes in part with GG-NER factors. Chromatin fractionation showed that the UV-dependent recruitment of CHD1 occurs to UV lesions in histone-assembled nucleosomal DNA and that this CHD1 relocation requires the lesion sensor XPC (xeroderma pigmentosum group C). In situ immunofluorescence analyses further demonstrate that CHD1 facilitates substrate handover from XPC to the downstream TFIIH (transcription factor IIH). Consequently, CHD1 depletion slows down CPD excision and sensitizes cells to UV-induced cytotoxicity. The finding of a CHD1-driven lesion handover between sequentially acting GG-NER factors on nucleosomal histone octamers suggests that chromatin provides a recognition scaffold enabling the detection of a subset of CPDs.
Timur Yusufzai - One of the best experts on this subject based on the ideXlab platform.
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Human CHD1 is required for early DNA-damage signaling and is uniquely regulated by its N terminus.
Nucleic acids research, 2018Co-Authors: Jia Zhou, Rodolfo Bortolozo Serafim, Steven Ketchum, Catarina G. Ferreira, Jessica C. Liu, Kathryn A. Coe, Brendan D. Price, Timur YusufzaiAbstract:CHD1 is a conserved chromatin remodeling enzyme required for development and linked to prostate cancer in adults, yet its role in human cells is poorly understood. Here, we show that targeted disruption of the CHD1 gene in human cells leads to a defect in early double-strand break (DSB) repair via homologous recombination (HR), resulting in hypersensitivity to ionizing radiation as well as PARP and PTEN inhibition. CHD1 knockout cells show reduced H2AX phosphorylation (γH2AX) and foci formation as well as impairments in CtIP recruitment to the damaged sites. Chromatin immunoprecipitation following a single DSB shows that the reduced levels of γH2AX accumulation at DSBs in CHD1-KO cells are due to both a global reduction in H2AX incorporation and poor retention of H2AX at the DSBs. We also identified a unique N-terminal region of CHD1 that inhibits the DNA binding, ATPase, and chromatin assembly and remodeling activities of CHD1. CHD1 lacking the N terminus was more active in rescuing the defects in γH2AX formation and CtIP recruitment in CHD1-KO cells than full-length CHD1, suggesting the N terminus is a negative regulator in cells. Our data point to a role for CHD1 in the DSB repair process and identify a novel regulatory region of the protein.
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Abstract 2433: Loss of chd5-mediated gene repression synergizes with MYCN to accelerate neuroblastoma tumorigenesis in zebrafish
Cancer Research, 2016Co-Authors: Mark W. Zimmerman, Jinhua Quan, Shuning He, Jimann Shin, Marc R. Mansour, Deepak Reyon, J. Keith Joung, Timur YusufzaiAbstract:Neuroblastoma is a malignancy of the peripheral sympathetic nervous system (PSNS) and accounts for 10-15% of cancer deaths among children. For the 40% of patients presenting with high-risk disease, current therapeutic approaches are insufficient and long-term survival is less than 50%. Along with genomic amplification of the MYCN oncogene, hemizygous loss of the 1p36 chromosomal region is a major risk factor in neuroblastoma. The human CHD5 gene is a neuronal specific chromatin remodeling helicase that maps to 1p36, and is thus frequently lost in high-risk neuroblastoma. Our laboratory has previously generated a faithful model of pediatric neuroblastoma in the zebrafish driven by overexpression of the MYCN oncogene in the PSNS (dbh:MYCN). Additionally, zebrafish chd5 mutant alleles were created using the newly developed gene editing technologies TALEN and CRISPR-Cas9. The resulting chd5 mutant fish exhibit abnormal development of the PSNS in the form of expansion of the superior cervical ganglia and enlargement of the interrenal gland (adrenal medulla). Haploinsufficiency for Chd5 combined with dbh:MYCN expression accelerates the onset and increases the penetrance of neuroblastoma tumorigenesis in zebrafish, indicating a tumor suppressive function. Elevated p-ERK and PCNA+ cells in tumor tissue indicates that loss of Chd5, cooperates with MYCN overexpression to accelerate neuroblast proliferation in vivo. Chd5 (in addition to Chd3 and Chd4) is a core member of the epigenetic regulatory NuRD complex, which also contains HDAC1-2, MTA1-3, MBD2-3, GATAD2A/B and RBBP4/7. The conserved biological function of Chd5 is to silence gene expression through the maintenance of a repressed chromatin state. Tumors deficient for Chd5 expression exhibit reduced levels of the H3K27me3 histone modification, a marker of facultatively repressed genes. Future studies will further explore the mechanism and function of Chd5 so that the pathways mediating tumor suppression can be elucidated and that essential proteins in these pathways can be targeted in ways that exploit the synthetic lethal relationships that are established. Citation Format: Mark W. Zimmerman, Shuning He, Jimann Shin, Shizhen Zhu, Feng Guo, Marc Mansour, Deepak Reyon, J Keith Joung, Jinhua Quan, Timur Yusufzai, A Thomas Look. Loss of chd5-mediated gene repression synergizes with MYCN to accelerate neuroblastoma tumorigenesis in zebrafish. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2433.
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the chromatin remodeling factor chd5 is a transcriptional repressor of wee1
PLOS ONE, 2014Co-Authors: Jinhua Quan, Guillaume Adelmant, Thomas A Look, Jarrod A Marto, Timur YusufzaiAbstract:Loss of the chromatin remodeling ATPase CHD5 has been linked to the progression of neuroblastoma tumors, yet the underlying mechanisms behind the tumor suppressor role of CHD5 are unknown. In this study, we purified the human CHD5 complex and found that CHD5 is a component of the full NuRD transcriptional repressor complex, which also contains methyl-CpG binding proteins and histone deacetylases. The CHD5/NuRD complex appears mutually exclusive with the related CHD4/NuRD complex as overexpression of CHD5 results in loss of the CHD4 protein in cells. Following a search for genes that are regulated by CHD5 in neuroblastoma cells, we found that CHD5 binds to and represses the G2/M checkpoint gene WEE1. Reintroduction of CHD5 into neuroblastoma cells represses WEE1 expression, demonstrating that CHD5 can function as a repressor in cells. A catalytically inactive mutant version of CHD5 is able to associate with a NuRD cofactor but fails to repress transcription. Our study shows that CHD5 is a NuRD-associated transcriptional repressor and identifies WEE1 as one of the CHD5-regulated genes that may link CHD5 to tumor suppression.
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the tumor suppressor chromodomain helicase dna binding protein 5 chd5 remodels nucleosomes by unwrapping
Journal of Biological Chemistry, 2014Co-Authors: Jinhua Quan, Timur YusufzaiAbstract:Although mutations or deletions of chromodomain helicase DNA-binding protein 5 (CHD5) have been linked to cancer and implicate CHD5 in tumor suppression, the ATP-dependent activity of CHD5 is currently unknown. In this study, we discovered that CHD5 is a chromatin remodeling factor with a unique enzymatic activity. CHD5 can expose nucleosomal DNA at one or two discrete positions in the nucleosome. The exposure of the nucleosomal DNA by CHD5 is dependent on ATP hydrolysis, but continued ATP hydrolysis is not required to maintain the nucleosomes in their remodeled state. The activity of CHD5 is distinct from other related chromatin remodeling ATPases, such as ACF and BRG1, and does not lead to complete disruption or destabilization of the nucleosome. Rather, CHD5 likely initiates remodeling in a manner similar to that of other remodeling factors but does not significantly reposition the nucleosome. While the related factor CHD4 shows strong ATPase activity, it does not unwrap nucleosomes as efficiently as CHD5. Our findings add to the growing evidence that chromatin remodeling ATPases have diverse roles in modulating chromatin structure.
Peter Rüthemann - One of the best experts on this subject based on the ideXlab platform.
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Chromatin remodeler CHD1 promotes XPC‐to‐TFIIH handover of nucleosomal UV lesions in nucleotide excision repair
The EMBO journal, 2017Co-Authors: Peter Rüthemann, Chiara Balbo Pogliano, Tamara Codilupi, Zuzana Garajova, Hanspeter NaegeliAbstract:Ultraviolet (UV) light induces mutagenic cyclobutane pyrimidine dimers (CPDs) in nucleosomal DNA that is tightly wrapped around histone octamers. How global-genome nucleotide excision repair (GG-NER) processes CPDs despite that this chromatin arrangement is poorly understood. An increased chromatin association of CHD1 (chromodomain helicase DNA-binding 1) upon UV irradiation indicated possible roles of this chromatin remodeler in the UV damage response. Immunoprecipitation of chromatin fragments revealed that CHD1 co-localizes in part with GG-NER factors. Chromatin fractionation showed that the UV-dependent recruitment of CHD1 occurs to UV lesions in histone-assembled nucleosomal DNA and that this CHD1 relocation requires the lesion sensor XPC (xeroderma pigmentosum group C). In situ immunofluorescence analyses further demonstrate that CHD1 facilitates substrate handover from XPC to the downstream TFIIH (transcription factor IIH). Consequently, CHD1 depletion slows down CPD excision and sensitizes cells to UV-induced cytotoxicity. The finding of a CHD1-driven lesion handover between sequentially acting GG-NER factors on nucleosomal histone octamers suggests that chromatin provides a recognition scaffold enabling the detection of a subset of CPDs.
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chromatin remodeler CHD1 promotes xpc to tfiih handover of nucleosomal uv lesions in nucleotide excision repair
The EMBO Journal, 2017Co-Authors: Peter Rüthemann, Chiara Balbo Pogliano, Tamara Codilupi, Zuzana Garajova, Hanspeter NaegeliAbstract:Ultraviolet (UV) light induces mutagenic cyclobutane pyrimidine dimers (CPDs) in nucleosomal DNA that is tightly wrapped around histone octamers. How global-genome nucleotide excision repair (GG-NER) processes CPDs despite that this chromatin arrangement is poorly understood. An increased chromatin association of CHD1 (chromodomain helicase DNA-binding 1) upon UV irradiation indicated possible roles of this chromatin remodeler in the UV damage response. Immunoprecipitation of chromatin fragments revealed that CHD1 co-localizes in part with GG-NER factors. Chromatin fractionation showed that the UV-dependent recruitment of CHD1 occurs to UV lesions in histone-assembled nucleosomal DNA and that this CHD1 relocation requires the lesion sensor XPC (xeroderma pigmentosum group C). In situ immunofluorescence analyses further demonstrate that CHD1 facilitates substrate handover from XPC to the downstream TFIIH (transcription factor IIH). Consequently, CHD1 depletion slows down CPD excision and sensitizes cells to UV-induced cytotoxicity. The finding of a CHD1-driven lesion handover between sequentially acting GG-NER factors on nucleosomal histone octamers suggests that chromatin provides a recognition scaffold enabling the detection of a subset of CPDs.