作者
Terence Gall-Duncan, Jennifer Luo, Carla-Marie Jurkovic, Laura A Fischer, Kyota Fujita, Amit L Deshmukh, Rachel J Harding, Stephanie Tran, Mustafa Mehkary, Vanessa Li, David E Leib, Ran Chen, Hikari Tanaka, Amanda G Mason, Dominique Lévesque, Mahreen Khan, Mortezaali Razzaghi, Tanya Prasolava, Stella Lanni, Nozomu Sato, Marie-Christine Caron, Gagan B Panigrahi, Peixiang Wang, Rachel Lau, Arturo López Castel, Jean-Yves Masson, Lynette Tippett, Clinton Turner, Maria Spies, Albert R La Spada, Eric I Campos, Maurice A Curtis, François-Michel Boisvert, Richard LM Faull, Beverly L Davidson, Masayuki Nakamori, Hitoshi Okazawa, Marc S Wold, Christopher E Pearson
发表日期
2023/10/26
期刊
Cell
卷号
186
期号
22
页码范围
4898-4919. e25
出版商
Elsevier
简介
Expansions of repeat DNA tracts cause >70 diseases, and ongoing expansions in brains exacerbate disease. During expansion mutations, single-stranded DNAs (ssDNAs) form slipped-DNAs. We find the ssDNA-binding complexes canonical replication protein A (RPA1, RPA2, and RPA3) and Alternative-RPA (RPA1, RPA3, and primate-specific RPA4) are upregulated in Huntington disease and spinocerebellar ataxia type 1 (SCA1) patient brains. Protein interactomes of RPA and Alt-RPA reveal unique and shared partners, including modifiers of CAG instability and disease presentation. RPA enhances in vitro melting, FAN1 excision, and repair of slipped-CAGs and protects against CAG expansions in human cells. RPA overexpression in SCA1 mouse brains ablates expansions, coincident with decreased ATXN1 aggregation, reduced brain DNA damage, improved neuron morphology, and rescued motor …
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T Gall-Duncan, J Luo, CM Jurkovic, LA Fischer, K Fujita… - Cell, 2023