The nucleosome-binding protein HMGN2 modulates global genome repair.
The HMGN family comprises nuclear proteins that bind to nucleosomes and alter the structure of chromatin. Here, we report that DT40 chicken cells lacking either HMGN2 or HMGN1a, or lacking both HMGN1a and HMGN2, are hypersensitive to killing by UV irradiation. Loss of both HMGN1a and HMGN2 or only HMGN2 increases the extent of UV-induced G(2)-M checkpoint arrest and the rate of apoptosis. HMGN null mutant cells showed slower removal of UV-induced DNA lesions from native chromatin, but the nucleotide excision repair remained intact, as measured by host cell reactivation assays. These results identify HMGN2 as a component of the global genome repair subpathway of the nucleotide excision repair pathway, and may indicate that HMGN2 facilitates the ability of the DNA repair proteins to access and repair UV-induced DNA lesions in chromatin. Our finding that HMGNs play a role in global DNA repair expands the role of these proteins in the maintenance of genome integrity.
Subramanian
Mangalam
M
Department of Biology, Texas Woman's University, Denton, TX 76204-5799, USA.
Gonzalez
Rhiannon W
RW
Patil
Hemangi
H
Ueda
Takahiro
T
Lim
Jae-Hwan
JH
Kraemer
Kenneth H
KH
Bustin
Michael
M
Bergel
Michael
M
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D026501:Blotting, Southwestern; D015153:Blotting, Western; D002453:Cell Cycle / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D002645:Chickens; D002843:Chromatin / Q000235:genetics; D004260:DNA Repair; D016678:Genome / Q000235:genetics*; D024241:HMGN1 Protein / Q000378:metabolism; D024242:HMGN2 Protein / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays
D002843:Chromatin; D024241:HMGN1 Protein; D024242:HMGN2 Protein