A method for nucleic acid synthesis and regeneration of a reusable synthesis initiator includes incorporating a linking nucleotide to an immobilized initiator using a polymerase, synthesizing a nucleic acid right after the linking nucleotide using the polymerase, subjecting a substrate base of the linking nucleotide in the nucleic acid to base-excision by a DNA glycosylase to generate an abasic site, subjecting the abasic site to cleavage by an endonuclease to release the nucleic acid from the initiator, and converting the 3′ terminus of the initiator back to its original form by a 3′ phosphatase activity-possessing enzyme. A kit based on the aforesaid method and a method for regenerating a reusable initiator are also disclosed.

Despite aggressive radio/chemotherapy regimens, pediatric high-grade gliomas (pHGG) are deadly brain tumors that remain incurable and are the leading cause of cancer-related death in children. By analysing the impact of H3.3 mutations on DNA repair and genome integrity maintenance capacities of glioma cells, the present inventors identified the PNKP enzyme as being a major protein partner interacting with mutated H3 oncohistone specifically, and involved in DNA aberrant repair. They showed that inhibition of this enzyme prevents the proliferation of glioma tumor cells bearing specific H3 oncohistone mutations. They therefore propose to target this enzyme in order to efficiently treat patients suffering from gliomas, in particular pediatric gliomas bearing these specific H3 oncohistone mutations, or to sensitize them to current radio/chemotherapeutic regimens, for which there is very limited response.