Mechanisms of Alternative Lengthening of Telomeres.
| Autor: | O'Sullivan RJ; Department of Pharmacology and Chemical Biology, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA rjo@pitt.edu rogergr@pennmedicine.upenn.edu., Greenberg RA; Department of Cancer Biology, Penn Center for Genome Integrity, Basser Center for BRCA, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA rjo@pitt.edu rogergr@pennmedicine.upenn.edu. |
|---|---|
| Jazyk: | angličtina |
| Zdroj: | Cold Spring Harbor perspectives in biology [Cold Spring Harb Perspect Biol] 2024 Nov 05. Date of Electronic Publication: 2024 Nov 05. |
| DOI: | 10.1101/cshperspect.a041690 |
| Abstrakt: | In recent years, significant advances have been made in understanding the intricate details of the mechanisms underlying alternative lengthening of telomeres (ALT). Studies of a specialized DNA strand break repair mechanism, known as break-induced replication, and the advent of telomere-specific DNA damaging strategies and proteomic methodologies to profile the ribonucleoprotein composition of telomeres enabled the discovery of networks of proteins that coordinate the stepwise homology-directed DNA repair and DNA synthesis processes of ALT. These networks couple mediators of homologous recombination, DNA template-switching, long-range template-directed DNA synthesis, and DNA strand resolution with SUMO-dependent liquid condensate formation to create discrete nuclear bodies where telomere extension occurs. This review will discuss the recent findings of how these networks may cooperate to mediate telomere extension by the ALT mechanism and their impact on telomere function and integrity in ALT cancer cells. (Copyright © 2024 Cold Spring Harbor Laboratory Press; all rights reserved.) |
| Databáze: | MEDLINE |
| Externí odkaz: |
|