The Contribution of Lysosomes to DNA Replication

Abstract

Lysosomes, acidic, membrane-bound organelles, are not only the core of the cellular recycling machinery, but they also serve as signaling hubs regulating various metabolic pathways. Lysosomes maintain energy homeostasis and provide pivotal substrates for anabolic processes, such as DNA replication. Every time the cell divides, its genome needs to be correctly duplicated; therefore, DNA replication requires rigorous regulation. Challenges that negatively affect DNA synthesis, such as nucleotide imbalance, result in replication stress with severe consequences for genome integrity. The lysosomal complex mTORC1 is directly involved in the synthesis of purines and pyrimidines to support DNA replication. Numerous drugs have been shown to target lysosomal function, opening an attractive avenue for new treatment strategies against various pathologies, including cancer. In this review, we focus on the interplay between lysosomal function and DNA replication through nucleic acid degradation and nucleotide biosynthesis and how these could be exploited for therapeutic purposes.

They Might Cut It—Lysosomes and Autophagy in Mitotic Progression

“…These findings stress the importance of coordinated enzymatic activities of cytoplasmic organelles in relation to a functional cell cycle. Although the idea of lysosomal contribution to the cell cycle control has already been presented in the 1960s, the study of lysosomal pathways has until recently focused mostly on interphase cells and the role of lysosomes in providing building blocks for DNA replication in the S phase of the cell cycle (Vanzo et al, 2020;Merchut-Maya and Maya-Mendoza, 2021). Here, we review the recent data on changes on lysosomes and the autophagic machinery during the cell cycle and their newly discovered roles in the control of cell division.…”

Lysosomes, curcumin, and anti-tumor effects: how are they linked?

“…S-adenosylmethionine sensor upstream of mTORC1 is a sensor for methionine, Sestrin2 for leucine, and cytosolic arginine sensor for MTORC subunit for arginine (Rebsamen et al, 2015;Wang et al, 2015;Lawrence and Zoncu, 2019). When cells sense abundant nutrients in these sensors, growth factors induce the phosphorylation of protein kinase B (AKT) and negatively regulate TSC complex subunit 2, activating the Rheb GTPase (Gwinn et al, 2008;Merchut-Maya and Maya-Mendoza, 2021). Amino acids can activate Rag GTPases by altering their binding to guanine nucleotides (Lin and Hardie, 2018).…”