김태헌 (The Hospital for Sick Children,University of Toronto, 현 Case Western Reserve University) | 한빛사논문 > 한빛사

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조회482

The Hospital for Sick Children,University of Toronto, 현 Case Western Reserve University

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Mol. Cell, January 11, 2024 | https://doi.org/10.1016/j.molcel.2023.12.019 Poly(ADP-ribosyl)ation enhances nucleosome dynamics and organizes DNA damage repair components within biomolecular condensates

Michael L. Nosella,^1,2,7 Tae Hun Kim,^1,2,3,4,7,8 Shuya Kate Huang,^1,2,3,4 Robert W. Harkness,^1,2,3,4 Monica Goncalves,⁵ Alisia Pan,¹ Maria Tereshchenko,² Siavash Vahidi,⁵ John L. Rubinstein,^1,2,6 Hyun O. Lee,²Julie D. Forman-Kay,^1,2,* and Lewis E. Kay ^1,2,3,4,9,*

¹Molecular Medicine Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada

²Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada

³Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada

⁴Department of Chemistry, University of Toronto, Toronto, ON M5S 1A8, Canada

⁵Department of Molecular and Cellular Biology, University of Guelph, Guelph, ON N1G 2W1, Canada

⁶Department of Medical Biophysics, University of Toronto, Toronto, ON M5S 1A8, Canada

⁷These authors contributed equally

⁸Present address: Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA

⁹Lead contact

^*Corresponding authors: correspondence to Julie D. Forman-Kay or Lewis E. Kay

Abstract

Nucleosomes, the basic structural units of chromatin, hinder recruitment and activity of various DNA repair proteins, necessitating modifications that enhance DNA accessibility. Poly(ADP-ribosyl)ation (PARylation) of proteins near damage sites is an essential initiation step in several DNA-repair pathways; however, its effects on nucleosome structural dynamics and organization are unclear. Using NMR, cryoelectron microscopy (cryo-EM), and biochemical assays, we show that PARylation enhances motions of the histone H3 tail and DNA, leaving the configuration of the core intact while also stimulating nuclease digestion and ligation of nicked nucleosomal DNA by LIG3. PARylation disrupted interactions between nucleosomes, preventing self-association. Addition of LIG3 and XRCC1 to PARylated nucleosomes generated condensates that selectively partition DNA repair-associated proteins in a PAR- and phosphorylation-dependent manner in vitro. Our results establish that PARylation influences nucleosomes across different length scales, extending from the atom-level motions of histone tails to the mesoscale formation of condensates with selective compositions.

논문정보

형식Research article
게재일2024년 01월 (BRIC 등록일 2024-01-15)
연구진국외 연구진
분야 생명과학 > 생화학

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