Abstract
DNA double-strand breaks (DSBs) are hazardous lesions that threaten genome integrity and cell survival. The DNA damage response (DDR) safeguards the genome by sensing DSBs, halting cell cycle progression and promoting repair through either non-homologous end joining (NHEJ) or homologous recombination (HR). The Mre11-Rad50-Xrs2/Nbs1 (MRX/N) complex is central to the DDR through its structural, enzymatic, and signaling roles. The complex tethers DNA ends, activates the Tel1/ATM kinase, resolves protein-bound or hairpin-capped DNA ends, and maintains telomere homeostasis. In addition to its role at DSBs, MRX/N associates with unperturbed replication forks, as well as stalled replication forks, to ensure complete DNA synthesis and to prevent chromosome rearrangements. Here, we summarize the significant progress made in characterizing the MRX/N complex and its various activities in chromosome metabolism.
Highlights
Genome integrity is constantly threatened by exogenous and endogenous stresses that can result in various types of DNA damage
Eukaryotic cells have evolved a sophisticated and highly conserved DNA damage response (DDR) system, which consists of a kinase cascade in response to lesion recognition coordinated with various repair mechanisms, to cope with Double-strand breaks (DSBs)
Mre11 and Rad50 are conserved in all domains of life whereas Xrs2/Nbs1 is less conserved than Mre11 and Rad50 and has only been identified in eukaryotes [2]
Summary
Genome integrity is constantly threatened by exogenous and endogenous stresses that can result in various types of DNA damage. Eukaryotic cells have evolved a sophisticated and highly conserved DNA damage response (DDR) system, which consists of a kinase cascade in response to lesion recognition coordinated with various repair mechanisms, to cope with DSBs. The Mre11-Rad50-Xrs2/Nbs complex (MRX in budding yeast, MRN in organisms with Nbs replacing Xrs2) orchestrates all stages of the DDR, including sensing the initial lesion, activating checkpoint signaling, driving specific repair pathways, and structurally bridging the participating DNA molecules together. The MRN complex is essential for cell viability, unlike in yeast, in which the identified null mutations are viable. In this we focusDNA on studies performed in S. cerevisiae in eukaryotes [2]. Components are associated with Nijmegen breakage syndrome (NBS), NBS-like disorder and ataxia disorder (ATLD), which are characterized by cellular radiosensitivity, immune
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