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Title: Chaperoning HMGA2 protein protects stalled replication forks in stem and cancer cells
Authors: Goodman, Steven D.
Tjokro, Natalia O.
Yu, Haojie
Lim, Hong Hwa
Sathiyanathan, Padmapriya
Natarajan, Suchitra
Chew, Tian Wei
Klonisch, Thomas
Surana, Uttam
Dröge, Peter
Keywords: DRNTU::Science::Biological sciences
Issue Date: 2014
Source: Yu, H., Lim, H. H., Tjokro, N., Sathiyanathan, P., Natarajan, S., Chew, T. W., et al. (2014). Chaperoning HMGA2 protein protects stalled replication forks in stem and cancer cells. Cell reports, 6, 1-14.
Series/Report no.: Cell reports
Abstract: Maintaining genome integrity requires the accurate and complete replication of chromosomal DNA. This is of the utmost importance for embryonic stem cells (ESCs), which differentiate into cells of all lineages, including germ cells. However, endogenous and exogenous factors frequently induce stalling of replication forks in every cell cycle, which can trigger mutations and chromosomal instabilities. We show here that the oncofetal, nonhistone chromatin factor HMGA2 equips cells with a highly effective first-line defense mechanism against endonucleolytic collapse of stalled forks. This fork-stabilizing function most likely employs scaffold formation at branched DNA via multiple DNA-binding domains. Moreover, HMGA2 works independently of other human factors in two heterologous cell systems to prevent DNA strand breaks. This fork chaperone function seemingly evolved to preserve ESC genome integrity. It is hijacked by tumor (stem) cells to also guard their genomes against DNA-damaging agents widely used to treat cancer patients.
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2014.01.014
Rights: © 2014 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative Works License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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