Publications

Fang TZ, Sun Y, Pearce AC, Eleuteri S, Kemp M, Luckhurst CA, Williams R, Mills R, Almond S, Burzynski L, Márkus NM, Lelliott CJ, Karp NA, Adams DJ, Jackson SP, Zhao JF, Ganley IG, Thompson PW, Balmus G and Simon DK.

Nature Communications 14(1):7295.

Mutations in SNCA, the gene encoding α-synuclein (αSyn), cause familial Parkinson's disease (PD) and aberrant αSyn is a key pathological hallmark of idiopathic PD. This α-synucleinopathy leads to mitochondrial dysfunction, which may drive dopaminergic neurodegeneration. PARKIN and PINK1, mutated in autosomal recessive PD, regulate the preferential autophagic clearance of dysfunctional mitochondria ("mitophagy") by inducing ubiquitylation of mitochondrial proteins, a process counteracted by deubiquitylation via USP30.

Kaisinger LR, Kentistou KA, Stankovic S, Gardner EJ, Day FR, Zhao Y, Mörseburg A, Carnie CJ, Zagnoli-Vieira G, Puddu F, Jackson SP, O’Rahilly S, I. Farooqi S, Dearden L, Pantaleão LC, Ozanne SE, Ong KK and Perry JRB.

Cell Genomics 3, 100362.

Obesity contributes substantially to the global burden of disease and has a significant heritable component. Recent large-scale exome sequencing studies identified several genes in which rare, protein-coding variants have large effects on adult body mass index (BMI). Here we extended such work by performing sex-stratified associations in the UK Biobank study (N∼420,000).

Serrano-Benitez A, Wells SE, Drummond-Clarke L, Russo LC, Thomas JC, Leal GA, Farrow M, Edgerton JM, Balasubramanian S, Yang M, Frezza C, Gautam A, Brazina J, Burdova K, Hoch NC, Jackson SP, Caldecott KW.

EMBO J. (2023) 42: e113190

DNA single-strand breaks (SSBs) disrupt DNA replication and induce chromosome breakage. However, whether SSBs induce chromosome breakage when present behind replication forks or ahead of replication forks is unclear. To address this question, we exploited an exquisite sensitivity of SSB repair-defective human cells lacking PARP activity or XRCC1 to the thymidine analogue 5-chloro-2′-deoxyuridine (CldU).

Awwad SW, Serrano-Benitez A, Thomas JC, Gupta V and Jackson SP.

Nature Reviews Molecular Cell Biology 24, 477–494

All organisms possess molecular mechanisms that govern DNA repair and associated DNA damage response (DDR) processes. Owing to their relevance to human disease, most notably cancer, these mechanisms have been studied extensively, yet new DNA repair and/or DDR factors and functional interactions between them are still being uncovered. The emergence of CRISPR technologies and CRISPR-based genetic screens has enabled genome-scale analyses of gene-gene and gene-drug interactions, thereby providing new insights into cellular processes in distinct DDR-deficiency genetic backgrounds and conditions.