醛缩酶A
DNA修复
生物
同源重组
DNA损伤
糖酵解
雷达51
果糖二磷酸醛缩酶
催化亚单位
磷酸二羟丙酮
DNA
自磷酸化
激酶
细胞生物学
分子生物学
生物化学
蛋白激酶A
酶
作者
Thais Sobanski,Amila Suraweera,Joshua T. Burgess,Iain A. Richard,Chee Man Cheong,Keyur A. Dave,Maddison Rose,Mark N. Adams,Kenneth J. O’Byrne,Derek J. Richard,Emma Bolderson
标识
DOI:10.1038/s41598-023-41133-1
摘要
Abstract Glucose metabolism and DNA repair are fundamental cellular processes frequently dysregulated in cancer. In this study, we define a direct role for the glycolytic Aldolase A (ALDOA) protein in DNA double-strand break (DSB) repair. ALDOA is a fructose biphosphate Aldolase that catalyses fructose-1,6-bisphosphate to glyceraldehyde 3-phosphate (G3P) and dihydroxyacetone phosphate (DHAP), during glycolysis. Here, we show that upon DNA damage induced by ionising radiation (IR), ALDOA translocates from the cytoplasm into the nucleus, where it partially co-localises with the DNA DSB marker γ-H2AX. DNA damage was shown to be elevated in ALDOA-depleted cells prior to IR and following IR the damage was repaired more slowly. Consistent with this, cells depleted of ALDOA exhibited decreased DNA DSB repair via non-homologous end-joining and homologous recombination. In support of the defective repair observed in its absence, ALDOA was found to associate with the major DSB repair effector kinases, DNA-dependent Protein Kinase (DNA-PK) and Ataxia Telangiectasia Mutated (ATM) and their autophosphorylation was decreased when ALDOA was depleted. Together, these data establish a role for an essential metabolic protein, ALDOA in DNA DSB repair and suggests that targeting ALDOA may enable the concurrent targeting of cancer metabolism and DNA repair to induce tumour cell death.
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