PARPs and ADP-ribosylation-mediated biomolecular condensates: determinants, dynamics, and disease implications

Trends in Biochemical Sciences, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 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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Deciphering the dark side of histone ADP-ribosylation: what structural features of damaged nucleosome regulate the activities of PARP1 and PARP2

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 30, 2025

ABSTRACT Poly(ADP-ribose) polymerases are critical enzymes contributing to regulation of numerous cellular processes, including DNA repair. Within the PARP family, PARP1 and PARP2 primarily facilitate PARylation in nucleus, particularly responding genotoxic stress. The activity PARPs is influenced by nature damage multiple protein partners, with HPF1 being important one. Forming a joint active site (PARP2), contributes histone following chromatin remodelling during stress events. This study elucidates interrelation between presence location one-nucleotide gap within nucleosome core particle (NCP) activities automodification heteromodification histones. Utilizing combination classical biochemical methods fluorescence-based technique single-molecule mass photometry approach, we have shown that NCP architecture impacts efficiency pattern ADP-ribosylation binding histones-associated damaged more significantly for than PARP1. Analysis based on existing studies HPF1-dependent ADP-ribosylome structural dynamics allows suggest conformational flexibility tails modulated post-translational modifications crucial delineating distinct roles responses. GRAPHICAL

Язык: Английский

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The zinc finger of DNA Ligase 3α binds to nucleosomes via an arginine anchor

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Март 10, 2025

Ligation of DNA single strand breaks is critical for maintaining genome integrity during replication and repair. Ligase III (LIG3α) forms an important complex with X-ray cross complementing protein 1 (XRCC1) break base excision We utilized a real time molecule approach to quantify binding kinetics Halo-tagged LIG3α XRCC1-YFP from nuclear extracts on long substrates containing nicks, nucleosomes or nicks embedded in nucleosomes. displayed higher affinity than XRCC1 the catalytic core N-terminal zinc finger (ZnF) competing nick engagement. Surprisingly, compared naked DNA, bound even more avidly undamaged nucleosome reconstituted 601-sequence, dependent two arginine residues ZnF. These studies reveal insights into detection identify role novel anchor engaging

Язык: Английский

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Recent advances in the synthesis of poly (ADP-ribose)

Bioorganic & Medicinal Chemistry, Год журнала: 2025, Номер unknown, С. 118202 - 118202

Опубликована: Апрель 1, 2025

Язык: Английский

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