DNA resection is a universal process in genome maintenance by which one strand of DNA is degraded, leaving the other strand intact. This sometimes highly processive process is critical for many forms of DNA damage repair, replication-coupled repair, meiotic recombination, and telomere maintenance. Therefore, resection must be tightly regulated to prevent genome instability and promote faithful and accurate repair. Here, we review what is known about how resection functions and how it is controlled, using DNA double-strand break repair and telomere maintenance as examples. We address how resection is regulated in three independent steps: resection initiation, long-range processing, and termination. By addressing these mechanisms in the context of both pathways, we attempt to provide an overview of the similarities as well as the outstanding questions regarding how this robust process is regulated.

DNA resection

DNA double-strand break

Telomere

DNA repair

Homologous recombination

Alternative end-joining

T-loops

© 2025 The Authors. Published by Elsevier B.V.