TY - JOUR
T1 - The architectural chromatin factor high mobility group A1 enhancesdna Ligase IV activity influencingdna repair
AU - Pellarin, Ilenia
AU - Arnoldo, Laura
AU - Costantini, Silvia
AU - Pegoraro, Silvia
AU - Ros, Gloria
AU - Penzo, Carlotta
AU - Triolo, Gianluca
AU - Demarchi, Francesca
AU - Sgarra, Riccardo
AU - Vindigni, Alessandro
AU - Manfioletti, Guidalberto
N1 - Publisher Copyright:
© 2016 Pellarin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2016/10
Y1 - 2016/10
N2 - The HMGA1 architectural transcription factor is an oncogene overexpressed in the vast majority of human cancers. HMGA1 is a highly connected node in the nuclear molecular network and the key aspect of HMGA1 involvement in cancer development is that HMGA1 simultaneously confers cells multiple oncogenic hits, ranging from global chromatin structural and gene expression modifications up to the direct functional alterations of key cellular proteins. Interestingly, HMGA1 also modulates DNA damage repair pathways. In this work, we provide evidences linking HMGA1 with Non-Homologous End Joining DNA repair. We show that HMGA1 is in complex with and is a substrate for DNA-PK. HMGA1 enhances Ligase IV activity and it counteracts the repressive histone H1 activity towards DNA ends ligation. Moreover, breast cancer cells overexpressing HMGA1 show a faster recovery upon induction of DNA double-strand breaks, which is associated with a higher survival. These data suggest that resistance to DNA-damaging agents in cancer cells could be partially attributed to HMGA1 overexpression thus highlighting the relevance of considering HMGA1 expression levels in the selection of valuable and effective pharmacological regimens.
AB - The HMGA1 architectural transcription factor is an oncogene overexpressed in the vast majority of human cancers. HMGA1 is a highly connected node in the nuclear molecular network and the key aspect of HMGA1 involvement in cancer development is that HMGA1 simultaneously confers cells multiple oncogenic hits, ranging from global chromatin structural and gene expression modifications up to the direct functional alterations of key cellular proteins. Interestingly, HMGA1 also modulates DNA damage repair pathways. In this work, we provide evidences linking HMGA1 with Non-Homologous End Joining DNA repair. We show that HMGA1 is in complex with and is a substrate for DNA-PK. HMGA1 enhances Ligase IV activity and it counteracts the repressive histone H1 activity towards DNA ends ligation. Moreover, breast cancer cells overexpressing HMGA1 show a faster recovery upon induction of DNA double-strand breaks, which is associated with a higher survival. These data suggest that resistance to DNA-damaging agents in cancer cells could be partially attributed to HMGA1 overexpression thus highlighting the relevance of considering HMGA1 expression levels in the selection of valuable and effective pharmacological regimens.
UR - http://www.scopus.com/inward/record.url?scp=84991475485&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0164258
DO - 10.1371/journal.pone.0164258
M3 - Article
C2 - 27723831
AN - SCOPUS:84991475485
SN - 1932-6203
VL - 11
JO - PloS one
JF - PloS one
IS - 10
M1 - e0164258
ER -