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.
journal_name
Cell Repjournal_title
Cell reportsauthors
Yu H,Lim HH,Tjokro NO,Sathiyanathan P,Natarajan S,Chew TW,Klonisch T,Goodman SD,Surana U,Dröge Pdoi
10.1016/j.celrep.2014.01.014subject
Has Abstractpub_date
2014-02-27 00:00:00pages
684-97issue
4issn
2211-1247pii
S2211-1247(14)00031-Xjournal_volume
6pub_type
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