The Role of Poly(ADP-ribose) Polymerase 1 in Nuclear and Mitochondrial Base Excision Repair

Biomolecules, Год журнала: 2023, Номер 13(8), С. 1195 - 1195

Опубликована: Июль 31, 2023

Poly(ADP-ribose) (PAR) Polymerase 1 (PARP-1), also known as ADP-ribosyl transferase with diphtheria toxin homology (ARTD-1), is a critical player in DNA damage repair, during which it catalyzes the ADP ribosylation of self and target enzymes. While nuclear localization PARP-1 has been well established, recent studies suggest its mitochondrial localization. In this review, we summarize differences between Base Excision Repair (BER) pathways, involvement BER, functional interplay other BER

Язык: Английский

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Asymmetric nucleosome PARylation at DNA breaks mediates directional nucleosome sliding by ALC1

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Фев. 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.

Язык: Английский

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Histone ADP-ribosylation promotes resistance to PARP inhibitors by facilitating PARP1 release from DNA lesions

Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(25)

Опубликована: Июнь 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.

Язык: Английский

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Role of PARP-1 structural and functional features in PARP-1 inhibitors development

Bioorganic Chemistry, Год журнала: 2025, Номер 156, С. 108188 - 108188

Опубликована: Янв. 21, 2025

Язык: Английский

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

Molecular Cell, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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