Bookcover of How dormant origins, the FA pathway and HELQ promote genome stability
Booktitle:

How dormant origins, the FA pathway and HELQ promote genome stability

LAP LAMBERT Academic Publishing (2014-10-16 )

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ISBN-13:

978-3-659-62223-6

ISBN-10:
3659622230
EAN:
9783659622236
Book language:
English
Blurb/Shorttext:
DNA replication is continually impeded by endogenous lesions that cause the stalling of replication forks. This threatens the integrity of the genome and may drive cancer development. Cells possess many mechanisms by which to deal with stalled forks including dormant (backup) origins, the Fanconi anemia pathway and the DNA helicase HELQ. However, their precise functions remained unclear. This book brings together multiple studies to shed light on how these mechanisms guard the genome. Using a unique mutant mouse model called Mcm4chaos3 exhibiting a decreased number of dormant origins, we provide evidence that origin-poor regions of the genome cannot finish replication until early M phase (or not all), leading to multiple forms of chromosome instability. A lack of dormant origins also leads to hyper-activation of the FA pathway, revealing its role in the recovery of stalled forks where origins are limited. Indeed, disruption of the FA pathway in Mcm4chaos3/chaos3 mice led to high perinatal lethality and accelerated tumor formation. Finally, we use the first Helq mutant mouse model to show that Helq works in parallel to the FA pathway to promote chromosome stability.
Publishing house:
LAP LAMBERT Academic Publishing
Website:
https://www.lap-publishing.com/
By (author) :
Spencer Luebben
Number of pages:
288
Published on:
2014-10-16
Stock:
Available
Category:
Genetics
Price:
82.90 €
Keywords:
Fanconi anemia, HELQ, dormant origins, chromosome instability, stalled fork, Cancer, DNA Replication

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