Radiation-induced genomic instability plays a vital role in carcinogenesis[1]. Bod1 is required for proper chro- mosome biorientation, and Bod1 depletion increases premature chromatid separation[2]. miR-142-3p inuence...Radiation-induced genomic instability plays a vital role in carcinogenesis[1]. Bod1 is required for proper chro- mosome biorientation, and Bod1 depletion increases premature chromatid separation[2]. miR-142-3p inuences cell cycle progression and inhibits proliferation and invasion in cervical carcinoma cells[3].展开更多
The clinical treatment of DNA-repair defective tumours has been revolutionised by the use of poly(ADP)ribose polymerase(PARP)inhibitors.However,the efficacy of these compounds is hampered by resistance,which is attrib...The clinical treatment of DNA-repair defective tumours has been revolutionised by the use of poly(ADP)ribose polymerase(PARP)inhibitors.However,the efficacy of these compounds is hampered by resistance,which is attributed to numerous mechanisms including rewiring of the DNA damage response to favour pathways that repair PARP inhibitor-mediated damage.Here,we comment on recent findings by our group identifying the lysine methyltransferase SETD1A as a novel factor that conveys PARPi resistance.We discuss the implications,with a particular focus on epigenetic modifications and H3K4 methylation.We also deliberate on the mechanisms responsible,the consequences for the refinement of PARP inhibitor use in the clinic,and future possibilities to circumvent drug resistance in DNA-repair deficient cancers.展开更多
文摘Radiation-induced genomic instability plays a vital role in carcinogenesis[1]. Bod1 is required for proper chro- mosome biorientation, and Bod1 depletion increases premature chromatid separation[2]. miR-142-3p inuences cell cycle progression and inhibits proliferation and invasion in cervical carcinoma cells[3].
基金supported by a PhD studentship from the University of Birmingham and Cancer Research UK(C17422/A25154)awarded to Sweatman E and Higgs MRa Breast Cancer Now project grant(2019AugPR1320)supporting Bayley R(awarded to Garcia P)an MRC Career Development Fellowship(MR/P009085/1)awarded to Higgs MR.
文摘The clinical treatment of DNA-repair defective tumours has been revolutionised by the use of poly(ADP)ribose polymerase(PARP)inhibitors.However,the efficacy of these compounds is hampered by resistance,which is attributed to numerous mechanisms including rewiring of the DNA damage response to favour pathways that repair PARP inhibitor-mediated damage.Here,we comment on recent findings by our group identifying the lysine methyltransferase SETD1A as a novel factor that conveys PARPi resistance.We discuss the implications,with a particular focus on epigenetic modifications and H3K4 methylation.We also deliberate on the mechanisms responsible,the consequences for the refinement of PARP inhibitor use in the clinic,and future possibilities to circumvent drug resistance in DNA-repair deficient cancers.
