Degradation of 5hmC-marked stalled replication forks by APE1 causes genomic instability
Suhas S. Kharat, Xia Ding, Divya Swaminathan, Akshey Suresh, Manish Singh, Satheesh Kumar Sengodan, Sandra Burkett, Hanna Marks, Chinmayi Pamala, Yafeng He, Stephen D. Fox, Eugen Buehler, Kathrin Muegge, Scott E. Martin, Shyam K. Sharan
Abstract
status. TET2 loss did not affect the recruitment of the repair protein RAD51 to sites of double-strand breaks (DSBs) or the abundance of proteins associated with RF integrity. The loss of TET2, of its product 5hmC, and of APE1 recruitment to stalled RFs promoted resistance to the chemotherapeutic cisplatin. Our findings reveal a previously unknown role for the epigenetic mark 5hmC in maintaining the integrity of stalled RFs and a potential resistance mechanism to PARPi and cisplatin.
Topics & Concepts
Genome instabilityCell biologyReplication (statistics)BiologyDegradation (telecommunications)GeneticsDNAVirologyDNA damageComputer scienceTelecommunicationsDNA Repair MechanismsCRISPR and Genetic EngineeringPARP inhibition in cancer therapy