Báo cáo khoa học: The protein shuffle Sequential interactions among components of the human nucleotide excision repair pathway

The protein shuffle

Tên đề tài: The protein shuffle: Sequential interactions among components of the human nucleotide excision repair pathway

Tác giả: Chin-Ju Park and Byong-Seok Choi

Lĩnh vực: Sinh học phân tử, Di truyền học

Nội dung tài liệu: Bài tổng quan này đi sâu vào cơ chế sửa chữa DNA bằng cách cắt bỏ nucleotide (NER) trong tế bào người, tập trung vào sự tương tác tuần tự giữa các thành phần của con đường này. NER là một quá trình sửa chữa DNA quan trọng để loại bỏ các tổn thương DNA lớn, và các protein liên quan đến bệnh xeroderma pigmentosum (XP) đóng vai trò trung tâm. Bài viết mô tả chi tiết cách các protein XP và các yếu tố liên quan khác như XPC-hHR23B, XPA-RPA, và XPF-ERCC1 tương tác với nhau để nhận diện, cắt bỏ và sửa chữa DNA bị tổn thương. Nghiên cứu này làm sáng tỏ mạng lưới điều hòa phức tạp và các tương tác phân tử giữa các yếu tố NER trong bối cảnh sửa chữa DNA.

Mục lục chi tiết:

• Keywords
• Correspondence
• Abbreviations
• Xeroderma pigmentosum (XP) is an inherited disease in which cells from patients exhibit defects in nucleotide excision repair (NER). XP proteins A-G are crucial in the processes of DNA damage recognition and incision, and patients with XP can carry mutations in any of the genes that specify these proteins. In mammalian cells, NER is a dynamic process in which a variety of proteins interact with one another, via modular domains, to carry out their functions. XP proteins are key players in several steps of the NER process, including DNA strand discrimination (XPA, in complex with replication protein A), repair complex formation (XPC, in complex with hHR23B; XPF, in complex with ERCC1) and repair factor recruitment (transcription factor IIH, in complex with XPG). Through these protein-protein interactions, various types of bulky DNA adducts can be recognized and repaired. Communication between the NER system and other cellular pathways is also achieved by selected binding of the various structural domains. Here, we summarize recent studies on the domain structures of human NER components and the regulatory networks that utilize these proteins. Data provided by these studies have helped to illuminate the complex molecular interactions among NER factors in the context of DNA repair.
• In mammalian cells, nucleotide excision repair (NER) is the major DNA repair pathway for the removal of bulky adducts induced by UV light or other environmental carcinogens [1-3]. NER proteins display both versatility and specificity in that they (a) recognize various types of DNA damage and (b) discriminate between these lesions and the abundant undamaged DNA present in the genome (including the intact DNA strand opposite the lesion). Depending on the precise location of the damaged DNA, the NER process is referred to as either transcription-coupled repair (TCR) or global genomic repair (GGR). The TCR process specifically repairs blemishes on the transcribed DNA strands of active genes, while GGR eliminates lesions from the entire genome. As defects in NER are known to cause inherited diseases, such as xeroderma pigmentosum (XP), it is crucial that researchers decipher the mechanisms of NER at the molecular level. XP proteins A-G (i.e. XPA, XPB, XPC, XPD, XPE, XPF and XPG) are known to participate in various
• NER reactions: an overview
• Damage recognition
• NER assembly
• Dual incision
• Damage excision
• Repair synthesis
• DNA ligation
• The XPC-hHR23B complex: a sensor of helical distortion
• XPC and its partners
• The protein shuffle
• TFIIH: shuttling between repair and transcription
• XPA-RPA: a linchpin of the NER network of interactions
• XPG and the XPF-ERCC1 complex: structure-specific nucleases
• Conclusion and perspectives
• Acknowledgements
• References