Interaction between RECQL4 and OGG1 promotes repair of oxidative base lesion 8-oxoG and is regulated by SIRT1 deacetylase.

Abstract

OGG1 initiated base excision repair (BER) is the major pathway for repair of oxidative DNA base damage 8-oxoguanine (8-oxoG). Here, we report that RECQL4 DNA helicase, deficient in the cancer-prone and premature aging Rothmund-Thomson syndrome, physically and functionally interacts with OGG1. RECQL4 promotes catalytic activity of OGG1 and RECQL4 deficiency results in defective 8-oxoG repair and increased genomic 8-oxoG. Furthermore, we show that acute oxidative stress leads to increased RECQL4 acetylation and its interaction with OGG1. The NAD+-dependent protein SIRT1 deacetylates RECQL4 in vitro and in cells thereby controlling the interaction between OGG1 and RECQL4 after DNA repair and maintaining RECQL4 in a low acetylated state. Collectively, we find that RECQL4 is involved in 8-oxoG repair through interaction with OGG1, and that SIRT1 indirectly modulates BER of 8-oxoG by controlling RECQL4-OGG1 interaction.

• Authors: Shunlei Duan, Xuerui Han, Mansour Akbari, Deborah L Croteau, Lene Juel Rasmussen, Vilhelm A Bohr
• Journal: Nucleic acids research (Nucleic Acids Res) Vol. 48 Issue 12 Pg. 6530-6546 (07 09 2020) ISSN: 1362-4962 [Electronic] England
• PMID: 32432680 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.

Chemical References

• Guanosine
• 8-hydroxyguanosine
• DNA Glycosylases
• oxoguanine glycosylase 1, human
• SIRT1 protein, human
• Sirtuin 1
• RECQL4 protein, human
• RecQ Helicases

Topics

• Acetylation
• Cell Line, Tumor
• DNA Glycosylases (metabolism)
• DNA Repair
• Guanosine (analogs & derivatives, genetics)
• HEK293 Cells
• Humans
• Oxidative Stress
• Protein Binding
• RecQ Helicases (metabolism)
• Sirtuin 1 (metabolism)