TISIDB

Summary
Symbol	RAD1
Name	RAD1 checkpoint DNA exonuclease
Aliases	HRAD1; REC1; exonuclease homolog RAD1; checkpoint control protein HRAD1; cell cycle checkpoint protein Hrad1 ......
Chromosomal Location	5p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Nucleus
Domain	PF02144 Repair protein Rad1/Rec1/Rad17
Function	Component of the 9-1-1 cell-cycle checkpoint response complex that plays a major role in DNA repair (PubMed:10846170, PubMed:10884395). The 9-1-1 complex is recruited to DNA lesion upon damage by the RAD17-replication factor C (RFC) clamp loader complex (PubMed:12578958). Acts then as a sliding clamp platform on DNA for several proteins involved in long-patch base excision repair (LP-BER) (PubMed:15871698). The 9-1-1 complex stimulates DNA polymerase beta (POLB) activity by increasing its affinity for the 3'-OH end of the primer-template and stabilizes POLB to those sites where LP-BER proceeds; endonuclease FEN1 cleavage activity on substrates with double, nick, or gap flaps of distinct sequences and lengths; and DNA ligase I (LIG1) on long-patch base excision repair substrates (PubMed:15314187, PubMed:15556996, PubMed:15871698). The 9-1-1 complex is necessary for the recruitment of RHNO1 to sites of double-stranded breaks (DSB) occurring during the S phase (PubMed:21659603). Isoform 1 possesses 3'->5' double stranded DNA exonuclease activity (PubMed:9660799).

> Gene Ontology [ TOP ]
Biological Process	GO:0000075 cell cycle checkpoint GO:0000077 DNA damage checkpoint GO:0006260 DNA replication GO:0007126 meiotic nuclear division GO:0009314 response to radiation GO:0010212 response to ionizing radiation GO:0010639 negative regulation of organelle organization GO:0010948 negative regulation of cell cycle process GO:0021762 substantia nigra development GO:0030901 midbrain development GO:0031570 DNA integrity checkpoint GO:0033313 meiotic cell cycle checkpoint GO:0040020 regulation of meiotic nuclear division GO:0045786 negative regulation of cell cycle GO:0045835 negative regulation of meiotic nuclear division GO:0048857 neural nucleus development GO:0051321 meiotic cell cycle GO:0051445 regulation of meiotic cell cycle GO:0051447 negative regulation of meiotic cell cycle GO:0051598 meiotic recombination checkpoint GO:0051783 regulation of nuclear division GO:0051784 negative regulation of nuclear division GO:0071214 cellular response to abiotic stimulus GO:0071478 cellular response to radiation GO:0071479 cellular response to ionizing radiation GO:0072331 signal transduction by p53 class mediator GO:0090305 nucleic acid phosphodiester bond hydrolysis GO:1901796 regulation of signal transduction by p53 class mediator GO:1903046 meiotic cell cycle process GO:2000241 regulation of reproductive process GO:2000242 negative regulation of reproductive process
Molecular Function	GO:0003684 damaged DNA binding GO:0004518 nuclease activity GO:0004527 exonuclease activity GO:0004529 exodeoxyribonuclease activity GO:0004536 deoxyribonuclease activity GO:0008408 3'-5' exonuclease activity GO:0008853 exodeoxyribonuclease III activity GO:0016796 exonuclease activity, active with either ribo- or deoxyribonucleic acids and producing 5'-phosphomonoesters GO:0016895 exodeoxyribonuclease activity, producing 5'-phosphomonoesters
Cellular Component	GO:0000793 condensed chromosome GO:0000794 condensed nuclear chromosome GO:0030896 checkpoint clamp complex GO:0044454 nuclear chromosome part

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-176187: Activation of ATR in response to replication stress R-HSA-1640170: Cell Cycle R-HSA-69620: Cell Cycle Checkpoints R-HSA-5693532: DNA Double-Strand Break Repair R-HSA-73894: DNA Repair R-HSA-69481: G2/M Checkpoints R-HSA-69473: G2/M DNA damage checkpoint R-HSA-74160: Gene Expression R-HSA-212436: Generic Transcription Pathway R-HSA-5693567: HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA) R-HSA-5685942: HDR through Homologous Recombination (HRR) R-HSA-5685938: HDR through Single Strand Annealing (SSA) R-HSA-5693579: Homologous DNA Pairing and Strand Exchange R-HSA-5693538: Homology Directed Repair R-HSA-5693616: Presynaptic phase of homologous DNA pairing and strand exchange R-HSA-5693607: Processing of DNA double-strand break ends R-HSA-5633007: Regulation of TP53 Activity R-HSA-6804756: Regulation of TP53 Activity through Phosphorylation R-HSA-3700989: Transcriptional Regulation by TP53

> KEGG and Reactome Pathway

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KEGG

Reactome

R-HSA-176187: Activation of ATR in response to replication stress
R-HSA-1640170: Cell Cycle
R-HSA-69620: Cell Cycle Checkpoints
R-HSA-5693532: DNA Double-Strand Break Repair
R-HSA-73894: DNA Repair
R-HSA-69481: G2/M Checkpoints
R-HSA-69473: G2/M DNA damage checkpoint
R-HSA-74160: Gene Expression
R-HSA-212436: Generic Transcription Pathway
R-HSA-5693567: HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA)
R-HSA-5685942: HDR through Homologous Recombination (HRR)
R-HSA-5685938: HDR through Single Strand Annealing (SSA)
R-HSA-5693579: Homologous DNA Pairing and Strand Exchange
R-HSA-5693538: Homology Directed Repair
R-HSA-5693616: Presynaptic phase of homologous DNA pairing and strand exchange
R-HSA-5693607: Processing of DNA double-strand break ends
R-HSA-5633007: Regulation of TP53 Activity
R-HSA-6804756: Regulation of TP53 Activity through Phosphorylation
R-HSA-3700989: Transcriptional Regulation by TP53

Summary
Symbol	RAD1
Name	RAD1 checkpoint DNA exonuclease
Aliases	HRAD1; REC1; exonuclease homolog RAD1; checkpoint control protein HRAD1; cell cycle checkpoint protein Hrad1 ......
Chromosomal Location	5p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between RAD1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining [ TOP ]
There is no record.

Summary
Symbol	RAD1
Name	RAD1 checkpoint DNA exonuclease
Aliases	HRAD1; REC1; exonuclease homolog RAD1; checkpoint control protein HRAD1; cell cycle checkpoint protein Hrad1 ......
Chromosomal Location	5p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of RAD1 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	Second most enriched score: 0.68	Sensitive to T cell-mediated killing
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	RAD1
Name	RAD1 checkpoint DNA exonuclease
Aliases	HRAD1; REC1; exonuclease homolog RAD1; checkpoint control protein HRAD1; cell cycle checkpoint protein Hrad1 ......
Chromosomal Location	5p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of RAD1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-0.162	0.376
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.177	0.892
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.158	0.883
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.311	0.379
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.344	0.791
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.272	0.867
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.113	0.741
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.194	0.899
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.009	0.996
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.813	0.508
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	-0.479	0.782
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.258	0.00136

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of RAD1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	1.4	-1.4	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	1.7	-1.7	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	11.8	-7	0.577
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	7.7	18.2	-10.5	0.576
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	RAD1
Name	RAD1 checkpoint DNA exonuclease
Aliases	HRAD1; REC1; exonuclease homolog RAD1; checkpoint control protein HRAD1; cell cycle checkpoint protein Hrad1 ......
Chromosomal Location	5p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of RAD1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	RAD1
Name	RAD1 checkpoint DNA exonuclease
Aliases	HRAD1; REC1; exonuclease homolog RAD1; checkpoint control protein HRAD1; cell cycle checkpoint protein Hrad1 ......
Chromosomal Location	5p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of RAD1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by RAD1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	RAD1
Name	RAD1 checkpoint DNA exonuclease
Aliases	HRAD1; REC1; exonuclease homolog RAD1; checkpoint control protein HRAD1; cell cycle checkpoint protein Hrad1 ......
Chromosomal Location	5p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of RAD1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	RAD1
Name	RAD1 checkpoint DNA exonuclease
Aliases	HRAD1; REC1; exonuclease homolog RAD1; checkpoint control protein HRAD1; cell cycle checkpoint protein Hrad1 ......
Chromosomal Location	5p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of RAD1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	RAD1
Name	RAD1 checkpoint DNA exonuclease
Aliases	HRAD1; REC1; exonuclease homolog RAD1; checkpoint control protein HRAD1; cell cycle checkpoint protein Hrad1 ......
Chromosomal Location	5p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between RAD1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	RAD1
Name	RAD1 checkpoint DNA exonuclease
Aliases	HRAD1; REC1; exonuclease homolog RAD1; checkpoint control protein HRAD1; cell cycle checkpoint protein Hrad1 ......
Chromosomal Location	5p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting RAD1 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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