SETD1A Methyltransferase Is Physically and Functionally Linked to the DNA Damage Repair Protein RAD18.
DNA Damage
DNA Repair
DNA-Binding Proteins
/ metabolism
Down-Regulation
HEK293 Cells
Histone-Lysine N-Methyltransferase
/ metabolism
Histones
/ metabolism
Humans
Lysine
/ metabolism
Methylation
Phenotype
Protein Binding
Protein Interaction Maps
Protein Subunits
/ metabolism
Proteomics
RNA, Messenger
/ genetics
Ubiquitin-Protein Ligases
/ metabolism
DNA damage repair
Epigenetics
Macromolecular complex analysis
Methylation*
Proliferation*
Protein-Protein Interactions*
SET/MLL Complex
Journal
Molecular & cellular proteomics : MCP
ISSN: 1535-9484
Titre abrégé: Mol Cell Proteomics
Pays: United States
ID NLM: 101125647
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
22
04
2019
pubmed:
12
5
2019
medline:
17
1
2020
entrez:
12
5
2019
Statut:
ppublish
Résumé
SETD1A is a SET domain-containing methyltransferase involved in epigenetic regulation of transcription. It is the main catalytic component of a multiprotein complex that methylates lysine 4 of histone H3, a histone mark associated with gene activation. In humans, six related protein complexes with partly nonredundant cellular functions share several protein subunits but are distinguished by unique catalytic SET-domain proteins. We surveyed physical interactions of the SETD1A-complex using endogenous immunoprecipitation followed by label-free quantitative proteomics on three subunits: SETD1A, RBBP5, and ASH2L. Surprisingly, SETD1A, but not RBBP5 or ASH2L, was found to interact with the DNA damage repair protein RAD18. Reciprocal RAD18 immunoprecipitation experiments confirmed the interaction with SETD1A, whereas size exclusion and protein network analysis suggested an interaction independent of the main SETD1A complex. We found evidence of SETD1A and RAD18 influence on mutual gene expression levels. Further, knockdown of the genes individually showed a DNA damage repair phenotype, whereas simultaneous knockdown resulted in an epistatic effect. This adds to a growing body of work linking epigenetic enzymes to processes involved in genome stability.
Identifiants
pubmed: 31076518
pii: S1535-9476(20)31549-8
doi: 10.1074/mcp.RA119.001518
pmc: PMC6601208
pii:
doi:
Substances chimiques
DNA-Binding Proteins
0
Histones
0
Protein Subunits
0
RAD18 protein, human
0
RNA, Messenger
0
Histone-Lysine N-Methyltransferase
EC 2.1.1.43
Setd1A protein, human
EC 2.1.1.43
Ubiquitin-Protein Ligases
EC 2.3.2.27
Lysine
K3Z4F929H6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1428-1436Informations de copyright
© 2019 Alsulami et al.
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