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|Title:||Chaperoning HMGA2 protein protects stalled replication forks in stem and cancer cells||Authors:||Goodman, Steven D.
Tjokro, Natalia O.
Lim, Hong Hwa
Chew, Tian Wei
|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.||URI:||https://hdl.handle.net/10356/102195
|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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