TY - JOUR
T1 - Regulation of cell differentiation by the DNA damage response
AU - Sherman, Mara H.
AU - Bassing, Craig H.
AU - Teitell, Michael A.
N1 - Funding Information:
Work in the Bassing and Teitell labs is supported by grants from the National Institutes of Health (GM07185 to M.H.S., CA136470 and CA125195 to C.H.B., and CA90571, CA156674, GM073981, P01GM081621, and PNEY018228 to M.A.T.) and by the California Institute for Regenerative Medicine (CIRM grant RB1-01397 to M.A.T.). C.H.B. is a Leukemia and Lymphoma Society Scholar.
PY - 2011/5
Y1 - 2011/5
N2 - When faced with DNA double-strand breaks (DSBs), vertebrate cells activate DNA damage response (DDR) programs that preserve genome integrity and suppress malignant transformation. Three established outcomes of the DDR include transient cell cycle arrest coupled with DNA repair, apoptosis, or senescence. However, recent studies in normal and cancer precursor or stem cells suggest that a fourth potential outcome, cell differentiation, is under the influence of DDR programs. Here we review and discuss the emerging evidence that supports the linkage of signaling from DSBs to the regulation of differentiation, including some of the molecular mechanisms driving this under-appreciated DDR outcome. We also consider the physiologic and pathologic consequences of defects in DDR signaling on cell differentiation and malignant transformation.
AB - When faced with DNA double-strand breaks (DSBs), vertebrate cells activate DNA damage response (DDR) programs that preserve genome integrity and suppress malignant transformation. Three established outcomes of the DDR include transient cell cycle arrest coupled with DNA repair, apoptosis, or senescence. However, recent studies in normal and cancer precursor or stem cells suggest that a fourth potential outcome, cell differentiation, is under the influence of DDR programs. Here we review and discuss the emerging evidence that supports the linkage of signaling from DSBs to the regulation of differentiation, including some of the molecular mechanisms driving this under-appreciated DDR outcome. We also consider the physiologic and pathologic consequences of defects in DDR signaling on cell differentiation and malignant transformation.
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U2 - 10.1016/j.tcb.2011.01.004
DO - 10.1016/j.tcb.2011.01.004
M3 - Review article
C2 - 21354798
AN - SCOPUS:79955531604
SN - 0962-8924
VL - 21
SP - 312
EP - 319
JO - Trends in Cell Biology
JF - Trends in Cell Biology
IS - 5
ER -