Role of condensates in modulating DNA repair pathways and its implication for chemoresistance

被引:19
作者
Dall'Agnese, Giuseppe [1 ,2 ]
Dall'Agnese, Alessandra [2 ]
Banani, Salman F. [2 ,3 ]
Codrich, Marta [1 ]
Malfatti, Matilde Clarissa [1 ]
Antoniali, Giulia [1 ]
Tell, Gianluca [1 ]
机构
[1] Univ Udine, Dept Med, Lab Mol Biol & DNA Repair, Udine, Italy
[2] Whitehead Inst Biomed Res, Cambridge, MA USA
[3] Harvard Med Sch, Brigham & Womens Hosp, Dept Pathol, Boston, MA USA
关键词
LIQUID PHASE-SEPARATION; BASE EXCISION-REPAIR; PRION-LIKE DOMAINS; DAMAGE RESPONSE; NUCLEAR-PORES; BINDING; POLY(ADP-RIBOSE); PROTEINS; CANCER; RNA;
D O I
10.1016/j.jbc.2023.104800
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
For cells, it is important to repair DNA damage, such as double-strand and single-strand DNA breaks, because unre-paired DNA can compromise genetic integrity, potentially leading to cell death or cancer. Cells have multiple DNA damage repair pathways that have been the subject of detailed genetic, biochemical, and structural studies. Recently, the sci-entific community has started to gain evidence that the repair of DNA double-strand breaks may occur within biomolecular condensates and that condensates may also contribute to DNA damage through concentrating genotoxic agents used to treat various cancers. Here, we summarize key features of biomole-cular condensates and note where they have been implicated in the repair of DNA double-strand breaks. We also describe ev-idence suggesting that condensates may be involved in the repair of other types of DNA damage, including single-strand DNA breaks, nucleotide modifications (e.g., mismatch and oxidized bases), and bulky lesions, among others. Finally, we discuss old and new mysteries that could now be addressed considering the properties of condensates, including chemo-resistance mechanisms.
引用
收藏
页数:13
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