XRCC1 mediates PARP1- and PAR-dependent recruitment of PARP2 to DNA damage sites.

 0 Người đánh giá. Xếp hạng trung bình 0

Tác giả: Seema Khattri Bhandari, Nicolas Call, Xiaoyu Huang, Brian J Lee, Kay Sze Karina Leung, Xiaohui Lin, Alan E Tomkinson, Kaitlynn F Wolfe, Shan Zha

Ngôn ngữ: eng

Ký hiệu phân loại:

Thông tin xuất bản: England : Nucleic acids research , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 468924

Poly-ADP-ribose polymerases 1 and 2 (PARP1 and 2) are critical sensors of DNA-strand breaks and targets for cancer therapy. Upon DNA damage, PARP1 and 2 synthesize poly-ADP-ribose (PAR) chains on themselves and other substrates, facilitating DNA single-strand break repair by recruiting PAR-binding DNA repair factors, including X-ray repair cross-complementing group 1 (XRCC1) and aprataxin and polynucleotide kinase phosphatase-like factor (APLF). While diverse DNA lesions activate PARP1, PARP2 is selectively activated by 5' phosphorylated nicks. They function independently and compensate for each other. Previous studies suggest that PARP1 and its PAR chains act upstream to recruit PARP2 to DNA damage sites. Here, we report that the scaffold protein XRCC1 mediates PARP1- and PAR-dependent recruitment of PARP2 to damage sites. XRCC1-deficiency causes hyperactivation of PARP1 while attenuating micro-irradiation-induced PARP2 foci. Mechanistically, the BRCT1 domain of XRCC1 binds to PAR, while its BRCT2 domain interacts with the PARP2 catalytic domain independently of the PARP2 enzymatic activity and the LIG3 BRCT domain via residues D575 and Y576. This mode of PARP2 enrichment is important for the recruitment of certain PAR-binding proteins, such as APLF, but dispensable for others, such as the XRCC1-BRCT1 domain. These findings highlight the distinct role of PARP1 and PARP2 in PAR synthesis and uncover unexpected hierarchical roles of PARP1 and XRCC1 upstream of PARP2.
Tạo bộ sưu tập với mã QR

THƯ VIỆN - TRƯỜNG ĐẠI HỌC CÔNG NGHỆ TP.HCM

ĐT: (028) 36225755 | Email: tt.thuvien@hutech.edu.vn

Copyright @2024 THƯ VIỆN HUTECH