Ultraviolet Damage and Repair Maps in Reveal the Impact of Domain-specific Changes in Nucleosome Repeat Length on Repair Efficiency

Overview

Journal Genome Res

Specialty Genetics

Date 2025 Jan 6

PMID 39762049

Authors

Benjamin Morledge-Hampton

Kathiresan Selvam

Manish Chauhan

Alan Goodman

Alan G Goodman

John J Wyrick

Affiliations

Soon will be listed here.

Abstract

Cyclobutane pyrimidine dimers (CPDs) are formed in DNA following exposure to ultraviolet (UV) light and are mutagenic unless repaired by nucleotide excision repair (NER). It is known that CPD repair rates vary in different genome regions owing to transcription-coupled NER and differences in chromatin accessibility; however, the impact of regional chromatin organization on CPD formation remains unclear. Furthermore, nucleosomes are known to modulate UV damage and repair activity, but how these damage and repair patterns are affected by the overarching chromatin domains in which these nucleosomes are located is not understood. Here, we generated a new CPD damage map in S2 cells using CPD-seq and analyzed it alongside existing excision repair-sequencing (XR-seq) data to compare CPD damage formation and repair rates across five previously established chromatin types in This analysis revealed that repair activity varies substantially across different chromatin types, whereas CPD formation is relatively unaffected. Moreover, we observe distinct patterns of repair activity in nucleosomes located in different chromatin types, which we show is owing to domain-specific differences in nucleosome repeat length (NRL). These findings indicate that NRL is altered in different chromatin types in and that changes in NRL modulate the repair of UV lesions.

References

Garcia-Nieto P, Schwartz E, King D, Paulsen J, Collas P, Herrera R . Carcinogen susceptibility is regulated by genome architecture and predicts cancer mutagenesis. EMBO J. 2017; 36(19):2829-2843. PMC: 5623849. DOI: 10.15252/embj.201796717. View

Gaillard H, Fitzgerald D, Smith C, Peterson C, Richmond T, Thoma F . Chromatin remodeling activities act on UV-damaged nucleosomes and modulate DNA damage accessibility to photolyase. J Biol Chem. 2003; 278(20):17655-63. DOI: 10.1074/jbc.M300770200. View

Hu J, Adebali O, Adar S, Sancar A . Dynamic maps of UV damage formation and repair for the human genome. Proc Natl Acad Sci U S A. 2017; 114(26):6758-6763. PMC: 5495279. DOI: 10.1073/pnas.1706522114. View

Rodriguez Y, Hinz J, Smerdon M . Accessing DNA damage in chromatin: Preparing the chromatin landscape for base excision repair. DNA Repair (Amst). 2015; 32:113-119. PMC: 4522338. DOI: 10.1016/j.dnarep.2015.04.021. View

Chaouch A, Lasko P . : a fruitful model for oncohistones. Fly (Austin). 2021; 15(1):28-37. PMC: 7808415. DOI: 10.1080/19336934.2020.1863124. View

Ujfaludi Z, Boros I, Balint E . Different sets of genes are activated by p53 upon UV or ionizing radiation in Drosophila melanogaster. Acta Biol Hung. 2008; 58 Suppl:65-79. DOI: 10.1556/ABiol.58.2007.Suppl.6. View

Clapier C, Chakravarthy S, Petosa C, Fernandez-Tornero C, Luger K, Muller C . Structure of the Drosophila nucleosome core particle highlights evolutionary constraints on the H2A-H2B histone dimer. Proteins. 2007; 71(1):1-7. PMC: 2443955. DOI: 10.1002/prot.21720. View

Eriksson P, Clark D . The yeast ISW1b ATP-dependent chromatin remodeler is critical for nucleosome spacing and dinucleosome resolution. Sci Rep. 2021; 11(1):4195. PMC: 7892562. DOI: 10.1038/s41598-021-82842-9. View

Selvam K, Plummer D, Mao P, Wyrick J . Set2 histone methyltransferase regulates transcription coupled-nucleotide excision repair in yeast. PLoS Genet. 2022; 18(3):e1010085. PMC: 8936446. DOI: 10.1371/journal.pgen.1010085. View

10.

Langmead B, Salzberg S . Fast gapped-read alignment with Bowtie 2. Nat Methods. 2012; 9(4):357-9. PMC: 3322381. DOI: 10.1038/nmeth.1923. View

11.

Gonzalez-Perez A, Sabarinathan R, Lopez-Bigas N . Local Determinants of the Mutational Landscape of the Human Genome. Cell. 2019; 177(1):101-114. DOI: 10.1016/j.cell.2019.02.051. View

12.

Quinlan A, Hall I . BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics. 2010; 26(6):841-2. PMC: 2832824. DOI: 10.1093/bioinformatics/btq033. View

13.

Cui F, Zhurkin V . Structure-based analysis of DNA sequence patterns guiding nucleosome positioning in vitro. J Biomol Struct Dyn. 2010; 27(6):821-41. PMC: 2993692. DOI: 10.1080/073911010010524947. View

14.

Selvam K, Sivapragasam S, Poon G, Wyrick J . Detecting recurrent passenger mutations in melanoma by targeted UV damage sequencing. Nat Commun. 2023; 14(1):2702. PMC: 10175485. DOI: 10.1038/s41467-023-38265-3. View

15.

Morledge-Hampton B, Wyrick J . Mutperiod: Analysis of periodic mutation rates in nucleosomes. Comput Struct Biotechnol J. 2021; 19:4177-4183. PMC: 8349767. DOI: 10.1016/j.csbj.2021.07.025. View

16.

Nalabothula N, McVicker G, Maiorano J, Martin R, Pritchard J, Fondufe-Mittendorf Y . The chromatin architectural proteins HMGD1 and H1 bind reciprocally and have opposite effects on chromatin structure and gene regulation. BMC Genomics. 2014; 15:92. PMC: 3928079. DOI: 10.1186/1471-2164-15-92. View

17.

Brash D . UV signature mutations. Photochem Photobiol. 2014; 91(1):15-26. PMC: 4294947. DOI: 10.1111/php.12377. View

18.

Szerlong H, Hansen J . Nucleosome distribution and linker DNA: connecting nuclear function to dynamic chromatin structure. Biochem Cell Biol. 2011; 89(1):24-34. PMC: 3125042. DOI: 10.1139/O10-139. View

19.

Mao P, Wyrick J, Roberts S, Smerdon M . UV-Induced DNA Damage and Mutagenesis in Chromatin. Photochem Photobiol. 2016; 93(1):216-228. PMC: 5315636. DOI: 10.1111/php.12646. View

20.

Fan Y, Nikitina T, Zhao J, Fleury T, Bhattacharyya R, Bouhassira E . Histone H1 depletion in mammals alters global chromatin structure but causes specific changes in gene regulation. Cell. 2005; 123(7):1199-212. DOI: 10.1016/j.cell.2005.10.028. View