ATP-Dependent Chromatin Remodeler CSB Couples DNA Repair Pathways to Transcription with Implications for Cockayne Syndrome and Cancer Therapy DOI Creative Commons
Rabeya Bilkis, Robert J. Lake, Hua-Ying Fan

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(4), P. 239 - 239

Published: Feb. 7, 2025

Efficient DNA lesion repair is crucial for cell survival, especially within actively transcribed regions that contain essential genetic information. Additionally, breaks in of active transcription are prone to generating insertions and deletions, which hallmark features cancer genomes. Cockayne syndrome protein B (CSB) the sole ATP-dependent chromatin remodeler coupling pathways with transcription, leading more efficient transcription. CSB best known its function transcription-coupled nucleotide excision (TC-NER), a process rapidly removes helix-distorting lesions stall RNA polymerase II, such as those created by chemotherapeutic platinum compounds UV irradiation. In addition NER, has also been reported couple homologous recombination Most recently, shown single-strand break this review, we will discuss overlapping distinct mechanisms couples these different We how functions may account emerging roles an innovative target therapy.

Language: Английский

PARP enzyme de novo synthesis of protein-free poly(ADP-ribose) DOI
Marie-France Langelier,

Manija Mirhasan,

Karine Gilbert

et al.

Molecular Cell, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Language: Английский

Citations

5
Asymmetric nucleosome PARylation at DNA breaks mediates directional nucleosome sliding by ALC1 DOI Creative Commons
Luka Bačić, Guillaume Gaullier, Jugal Mohapatra

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Feb. 2, 2024

Abstract The chromatin remodeler ALC1 is activated by DNA damage-induced poly(ADP-ribose) deposited PARP1/PARP2 and their co-factor HPF1. has emerged as a cancer drug target, but how it recruited to ADP-ribosylated nucleosomes affect positioning near breaks unknown. Here we find that PARP1/HPF1 preferentially initiates ADP-ribosylation on the histone H2B tail closest break. To dissect consequences of such asymmetry, generate with defined one side only. cryo-electron microscopy structure bound an asymmetric nucleosome indicates preferential engagement side. Using single-molecule FRET, demonstrate this recruitment gives rise directed sliding away from linker site. Our data suggest mechanism which slides break render more accessible repair factors.

Language: Английский

Citations

4
Histone ADP-ribosylation promotes resistance to PARP inhibitors by facilitating PARP1 release from DNA lesions DOI Creative Commons
Siham Zentout, Victor Imburchia, Catherine Chapuis

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(25)

Published: June 12, 2024

Poly(ADP-ribose) polymerase 1 (PARP1) has emerged as a central target for cancer therapies due to the ability of PARP inhibitors specifically kill tumors deficient DNA repair by homologous recombination. Upon damage, PARP1 quickly binds breaks and triggers ADP-ribosylation signaling. is important recruitment various factors sites well timely dissociation from breaks. Indeed, becomes trapped at in presence inhibitors, mechanism underlying cytotoxitiy these inhibitors. Therefore, any cellular process influencing trapping thought impact inhibitor efficiency, potentially leading acquired resistance patients treated with drugs. There are numerous targets after including itself histones. While recent findings reported that automodification promotes its release lesions, potential other ADP-ribosylated proteins on this remains unknown. Here, we demonstrate histone also crucial dissipation thus contributing Considering crosstalk between marks, our open interesting perspectives development more efficient inhibitor-driven therapies.

Language: Английский

Citations

4
A PARP2 active site helix melts to permit DNA damage-induced enzymatic activation DOI

Emily S Smith-Pillet,

Ramya Billur, Marie-France Langelier

et al.

Molecular Cell, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
ATP-Dependent Chromatin Remodeler CSB Couples DNA Repair Pathways to Transcription with Implications for Cockayne Syndrome and Cancer Therapy DOI Creative Commons
Rabeya Bilkis, Robert J. Lake, Hua-Ying Fan

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(4), P. 239 - 239

Published: Feb. 7, 2025

Efficient DNA lesion repair is crucial for cell survival, especially within actively transcribed regions that contain essential genetic information. Additionally, breaks in of active transcription are prone to generating insertions and deletions, which hallmark features cancer genomes. Cockayne syndrome protein B (CSB) the sole ATP-dependent chromatin remodeler coupling pathways with transcription, leading more efficient transcription. CSB best known its function transcription-coupled nucleotide excision (TC-NER), a process rapidly removes helix-distorting lesions stall RNA polymerase II, such as those created by chemotherapeutic platinum compounds UV irradiation. In addition NER, has also been reported couple homologous recombination Most recently, shown single-strand break this review, we will discuss overlapping distinct mechanisms couples these different We how functions may account emerging roles an innovative target therapy.

Language: Английский

Citations

0