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Article

FAN1 exo- not endo-nuclease pausing on disease-associated slipped-DNA repeats: A mechanism of repeat instability.

Cell reports - 7 Dec 2021

Deshmukh Amit Laxmikant, Caron Marie-Christine, Mohiuddin Mohiuddin, Lanni Stella, Panigrahi Gagan B, Khan Mahreen, Engchuan Worrawat, Shum Natalie, Faruqui Aisha, Wang Peixiang, Yuen Ryan K C, Nakamori Masayuki, Nakatani Kazuhiko, Masson Jean-Yves, Pearson Christopher E

Abstract excerpt

Ongoing inchworm-like CAG and CGG repeat expansions in brains, arising by aberrant processing of slipped DNAs, may drive Huntington's disease, fragile X syndrome, and autism. FAN1 nuclease modifies hyper-expansion rates by unknown means. We show that FAN1, through iterative cycles, binds, dimerizes, and cleaves slipped DNAs, yielding striking exo-nuclease pauses along slip-outs: 5'-C↓A↓GC↓A↓G-3' and...

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PMID: 34879276
DOI: 10.1016/j.celrep.2021.110078

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