TY - JOUR
T1 - MiR-223-3p promotes genomic stability of hematopoietic progenitors after radiation
AU - Chen, Shi
AU - Srinivasan, Gayathri
AU - Jaiswal, Aruna
AU - Williamson, Elizabeth A.
AU - Li, Lingxiao
AU - Arris, Dominic
AU - Zhou, Daohong
AU - Xu, Mingjiang
AU - Hromas, Robert
N1 - Publisher Copyright:
© 2023 ISEH – Society for Hematology and Stem Cells
PY - 2024/1
Y1 - 2024/1
N2 - When hematopoietic cells are overwhelmed with ionizing radiation (IR) DNA damage, the alternative non-homologous end-joining (aNHEJ) repair pathway is activated to repair stressed replication forks. While aNHEJ can rescue cells overwhelmed with DNA damage, it can also mediate chromosomal deletions and fusions, which can cause mis-segregation in mitosis and resultant aneuploidy. We previously reported that a hematopoietic microRNA, miR-223-3p, normally represses aNHEJ. We found that miR-223−/− mice have increased survival of hematopoietic stem and progenitor cells (HSPCs) after sublethal IR. However, this came at the cost of significantly more genomic aberrancies, with miR-223−/− hematopoietic progenitors having increased metaphase aberrancies, including chromothripsis, and increased sequence abnormalities, especially deletions, which is consistent with aNHEJ. These data imply that when an HSPC is faced with substantial DNA damage, it may trade genomic damage for its own survival by choosing the aNHEJ repair pathway, and this choice is regulated in part by miR-223-3p.
AB - When hematopoietic cells are overwhelmed with ionizing radiation (IR) DNA damage, the alternative non-homologous end-joining (aNHEJ) repair pathway is activated to repair stressed replication forks. While aNHEJ can rescue cells overwhelmed with DNA damage, it can also mediate chromosomal deletions and fusions, which can cause mis-segregation in mitosis and resultant aneuploidy. We previously reported that a hematopoietic microRNA, miR-223-3p, normally represses aNHEJ. We found that miR-223−/− mice have increased survival of hematopoietic stem and progenitor cells (HSPCs) after sublethal IR. However, this came at the cost of significantly more genomic aberrancies, with miR-223−/− hematopoietic progenitors having increased metaphase aberrancies, including chromothripsis, and increased sequence abnormalities, especially deletions, which is consistent with aNHEJ. These data imply that when an HSPC is faced with substantial DNA damage, it may trade genomic damage for its own survival by choosing the aNHEJ repair pathway, and this choice is regulated in part by miR-223-3p.
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U2 - 10.1016/j.exphem.2023.10.002
DO - 10.1016/j.exphem.2023.10.002
M3 - Article
C2 - 37875176
AN - SCOPUS:85178239517
SN - 0301-472X
VL - 129
JO - Experimental Hematology
JF - Experimental Hematology
M1 - 104123
ER -