A Quantitative Modelling Approach for DNA Repair on a Population Scale

Overview

Journal PLoS Comput Biol

Specialty Biology

Date 2022 Sep 12

PMID 36094963

Authors

Leo Zeitler

Cyril Denby Wilkes

Arach Goldar

Julie Soutourina

Affiliations

Soon will be listed here.

Abstract

The great advances of sequencing technologies allow the in vivo measurement of nuclear processes-such as DNA repair after UV exposure-over entire cell populations. However, data sets usually contain only a few samples over several hours, missing possibly important information in between time points. We developed a data-driven approach to analyse CPD repair kinetics over time in Saccharomyces cerevisiae. In contrast to other studies that consider sequencing signals as an average behaviour, we understand them as the superposition of signals from independent cells. By motivating repair as a stochastic process, we derive a minimal model for which the parameters can be conveniently estimated. We correlate repair parameters to a variety of genomic features that are assumed to influence repair, including transcription rate and nucleosome density. The clearest link was found for the transcription unit length, which has been unreported for budding yeast to our knowledge. The framework hence allows a comprehensive analysis of nuclear processes on a population scale.

Citing Articles

The next-generation sequencing-chess problem.

Zeitler L, Goldar A, Denby Wilkes C, Soutourina J NAR Genom Bioinform. 2024; 6(4):lqae144.

PMID: 39450311 PMC: 11500447. DOI: 10.1093/nargab/lqae144.

DNA lesion bypass and the stochastic dynamics of transcription-coupled repair.

Nicholson M, Anderson C, Odom D, Aitken S, Taylor M Proc Natl Acad Sci U S A. 2024; 121(20):e2403871121.

PMID: 38717857 PMC: 11098089. DOI: 10.1073/pnas.2403871121.

Correction: A quantitative modelling approach for DNA repair on a population scale.

PLoS Comput Biol. 2023; 19(10):e1011602.

PMID: 37889881 PMC: 10610071. DOI: 10.1371/journal.pcbi.1011602.

References

Kong M, Van Houten B . Rad4 recognition-at-a-distance: Physical basis of conformation-specific anomalous diffusion of DNA repair proteins. Prog Biophys Mol Biol. 2016; 127:93-104. PMC: 5462892. DOI: 10.1016/j.pbiomolbio.2016.12.004. View

Mellon I, Spivak G, HANAWALT P . Selective removal of transcription-blocking DNA damage from the transcribed strand of the mammalian DHFR gene. Cell. 1987; 51(2):241-9. DOI: 10.1016/0092-8674(87)90151-6. View

Hu J, Lieb J, Sancar A, Adar S . Cisplatin DNA damage and repair maps of the human genome at single-nucleotide resolution. Proc Natl Acad Sci U S A. 2016; 113(41):11507-11512. PMC: 5068337. DOI: 10.1073/pnas.1614430113. 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

Park D, Morris A, Battenhouse A, Iyer V . Simultaneous mapping of transcript ends at single-nucleotide resolution and identification of widespread promoter-associated non-coding RNA governed by TATA elements. Nucleic Acids Res. 2014; 42(6):3736-49. PMC: 3973313. DOI: 10.1093/nar/gkt1366. View

Tortora M, Salari H, Jost D . Chromosome dynamics during interphase: a biophysical perspective. Curr Opin Genet Dev. 2020; 61:37-43. DOI: 10.1016/j.gde.2020.03.001. View

Gong F, Fahy D, Smerdon M . Rad4-Rad23 interaction with SWI/SNF links ATP-dependent chromatin remodeling with nucleotide excision repair. Nat Struct Mol Biol. 2006; 13(10):902-7. DOI: 10.1038/nsmb1152. View

Oliveira G, Oravecz A, Kobi D, Maroquenne M, Bystricky K, Sexton T . Precise measurements of chromatin diffusion dynamics by modeling using Gaussian processes. Nat Commun. 2021; 12(1):6184. PMC: 8548522. DOI: 10.1038/s41467-021-26466-7. View

van Eijk P, Nandi S, Yu S, Bennett M, Leadbitter M, Teng Y . Nucleosome remodeling at origins of global genome-nucleotide excision repair occurs at the boundaries of higher-order chromatin structure. Genome Res. 2018; 29(1):74-84. PMC: 6314166. DOI: 10.1101/gr.237198.118. View

10.

Stauffer D, Schulze C, Heermann D . Superdiffusion in a model for diffusion in a molecularly crowded environment. J Biol Phys. 2009; 33(4):305-12. PMC: 2646401. DOI: 10.1007/s10867-008-9075-2. View

11.

Politi A, Mone M, Houtsmuller A, Hoogstraten D, Vermeulen W, Heinrich R . Mathematical modeling of nucleotide excision repair reveals efficiency of sequential assembly strategies. Mol Cell. 2005; 19(5):679-90. DOI: 10.1016/j.molcel.2005.06.036. View

12.

Luijsterburg M, von Bornstaedt G, Gourdin A, Politi A, Mone M, Warmerdam D . Stochastic and reversible assembly of a multiprotein DNA repair complex ensures accurate target site recognition and efficient repair. J Cell Biol. 2010; 189(3):445-63. PMC: 2867314. DOI: 10.1083/jcb.200909175. View

13.

Shimamoto N . One-dimensional diffusion of proteins along DNA. Its biological and chemical significance revealed by single-molecule measurements. J Biol Chem. 1999; 274(22):15293-6. DOI: 10.1074/jbc.274.22.15293. View

14.

Marteijn J, Lans H, Vermeulen W, Hoeijmakers J . Understanding nucleotide excision repair and its roles in cancer and ageing. Nat Rev Mol Cell Biol. 2014; 15(7):465-81. DOI: 10.1038/nrm3822. View

15.

Deaconescu A, Chambers A, Smith A, Nickels B, Hochschild A, Savery N . Structural basis for bacterial transcription-coupled DNA repair. Cell. 2006; 124(3):507-20. DOI: 10.1016/j.cell.2005.11.045. View

16.

Tufegdzic Vidakovic A, Mitter R, Kelly G, Neumann M, Harreman M, Rodriguez-Martinez M . Regulation of the RNAPII Pool Is Integral to the DNA Damage Response. Cell. 2020; 180(6):1245-1261.e21. PMC: 7103762. DOI: 10.1016/j.cell.2020.02.009. View

17.

Schmidt H, Sewitz S, Andrews S, Lipkow K . An integrated model of transcription factor diffusion shows the importance of intersegmental transfer and quaternary protein structure for target site finding. PLoS One. 2014; 9(10):e108575. PMC: 4204827. DOI: 10.1371/journal.pone.0108575. View

18.

Yu S, Evans K, van Eijk P, Bennett M, Webster R, Leadbitter M . Global genome nucleotide excision repair is organized into domains that promote efficient DNA repair in chromatin. Genome Res. 2016; 26(10):1376-1387. PMC: 5052058. DOI: 10.1101/gr.209106.116. View

19.

Sweder K, HANAWALT P . Preferential repair of cyclobutane pyrimidine dimers in the transcribed strand of a gene in yeast chromosomes and plasmids is dependent on transcription. Proc Natl Acad Sci U S A. 1992; 89(22):10696-700. PMC: 50408. DOI: 10.1073/pnas.89.22.10696. View

20.

Tran N, Qu P, Simpson D, Lindsey-Boltz L, Guan X, Schmitt C . In silico construction of a protein interaction landscape for nucleotide excision repair. Cell Biochem Biophys. 2009; 53(2):101-14. PMC: 2635916. DOI: 10.1007/s12013-009-9042-y. View