کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2077863 1079752 2010 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Hematopoietic Stem Cell Quiescence Promotes Error-Prone DNA Repair and Mutagenesis
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیوتکنولوژی یا زیست‌فناوری
پیش نمایش صفحه اول مقاله
Hematopoietic Stem Cell Quiescence Promotes Error-Prone DNA Repair and Mutagenesis
چکیده انگلیسی

SummaryMost adult stem cells, including hematopoietic stem cells (HSCs), are maintained in a quiescent or resting state in vivo. Quiescence is widely considered to be an essential protective mechanism for stem cells that minimizes endogenous stress caused by cellular respiration and DNA replication. We demonstrate that HSC quiescence can also have detrimental effects. We found that HSCs have unique cell-intrinsic mechanisms ensuring their survival in response to ionizing irradiation (IR), which include enhanced prosurvival gene expression and strong activation of p53-mediated DNA damage response. We show that quiescent and proliferating HSCs are equally radioprotected but use different types of DNA repair mechanisms. We describe how nonhomologous end joining (NHEJ)-mediated DNA repair in quiescent HSCs is associated with acquisition of genomic rearrangements, which can persist in vivo and contribute to hematopoietic abnormalities. Our results demonstrate that quiescence is a double-edged sword that renders HSCs intrinsically vulnerable to mutagenesis following DNA damage.

Graphical AbstractFigure optionsDownload high-quality image (170 K)Download as PowerPoint slideHighlights
► Long-lived HSCs have unique survival mechanisms
► Short-lived myeloid progenitors are poised to die
► Quiescent and proliferating HSCs use different mechanisms of DNA repair
► Quiescent HSCs are intrinsically vulnerable to mutagenesis

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 7, Issue 2, 6 August 2010, Pages 174–185
نویسندگان
, , , , , , , ,