Insights into Rad3 kinase recruitment from the crystal structure of the DNA damage checkpoint protein Rad26

TY - JOUR

T1 - Insights into Rad3 kinase recruitment from the crystal structure of the DNA damage checkpoint protein Rad26

AU - Andersen, Kasper Røjkjær

N1 - Copyright © 2017, The American Society for Biochemistry and Molecular Biology.

PY - 2017/5/19

Y1 - 2017/5/19

N2 - Metabolic products and environmental factors constantly damage DNA. To protect against these insults and maintain genome integrity, cells have evolved mechanisms to repairDNA lesions. One such mechanism involves Rad3, a master kinase coordinating the DNA damage response. Rad26 is a functional subunit of the Rad3-Rad26 complex and is responsible for bringing the kinase to sites of DNA damage. Here, I present the crystal structure of Rad26 and identify the elements important for recruiting Rad3. The structure suggests that Rad26 is a dimer with a conserved interface in the N-terminal part of the protein. Biochemical data showed that Rad26 uses its C-terminal domain and the flanking kinase-docking motif to bind specific HEAT repeats in Rad3. Analysis of the reconstituted Rad3- Rad26 heterotetrameric complex with electron microscopy enabled me to propose a structural model for its quaternary structure. In conclusion, these results suggest that Rad26 exists as a dimer and provide crucial insight into how Rad3 is recruited and incorporated into the Rad3-Rad26 DNA repair complex.

AB - Metabolic products and environmental factors constantly damage DNA. To protect against these insults and maintain genome integrity, cells have evolved mechanisms to repairDNA lesions. One such mechanism involves Rad3, a master kinase coordinating the DNA damage response. Rad26 is a functional subunit of the Rad3-Rad26 complex and is responsible for bringing the kinase to sites of DNA damage. Here, I present the crystal structure of Rad26 and identify the elements important for recruiting Rad3. The structure suggests that Rad26 is a dimer with a conserved interface in the N-terminal part of the protein. Biochemical data showed that Rad26 uses its C-terminal domain and the flanking kinase-docking motif to bind specific HEAT repeats in Rad3. Analysis of the reconstituted Rad3- Rad26 heterotetrameric complex with electron microscopy enabled me to propose a structural model for its quaternary structure. In conclusion, these results suggest that Rad26 exists as a dimer and provide crucial insight into how Rad3 is recruited and incorporated into the Rad3-Rad26 DNA repair complex.

KW - Journal Article

UR - http://www.scopus.com/inward/record.url?scp=85019579148&partnerID=8YFLogxK

U2 - 10.1074/jbc.M117.780189

DO - 10.1074/jbc.M117.780189

M3 - Journal article

C2 - 28314775

SN - 0021-9258

VL - 292

SP - 8149

EP - 8157

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 20

ER -