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protein coding gene - rad4 (SPAC23C4.18c) - BRCT domain protein Rad4

Gene summary

Standard name
rad4
Systematic ID
SPAC23C4.18c
Product
BRCT domain protein Rad4
Organism
Schizosaccharomyces pombe (fission yeast)
Synonyms
cut5, dre3, dpb11
UniProt ID
P32372
ORFeome ID
27/27F12
Characterisation status
biological role published
Feature type
mRNA gene
Genomic location
chromosome I: 1058646..1062912 reverse strand

Annotation

GO biological process

GO:0006325 - chromatin organization

References:

GO:0006270 - DNA replication initiation

References:

GO:0044773 - mitotic DNA damage checkpoint signaling

References:

GO:0033314 - mitotic DNA replication checkpoint signaling

References:

GO:0007095 - mitotic G2 DNA damage checkpoint signaling

References:

GO cellular component

GO:0070532 - BRCA1-B complex

References:

GO:0000785 - chromatin

References:

GO:0005829 - cytosol

References:

GO:0031261 - DNA replication preinitiation complex

References:

GO:0072686 - mitotic spindle

References:

GO:0044732 - mitotic spindle pole body

References:

GO:0005634 - nucleus

References:

GO:0035861 - site of double-strand break

References:

GO:0043596 - nuclear replication fork

References:

GO molecular function

GO:0140463 - chromatin-protein adaptor activity

References:

GO:0005515 - protein binding

References:

GO:0035591 - signaling adaptor activity

References:

Modification

MOD:00046 - O-phospho-L-serine

References:

MOD:00047 - O-phospho-L-threonine

References:

MOD:00696 - phosphorylated residue

References:

MOD:01148 - ubiquitinylated lysine

References:

Multi-locus phenotype

FYPO:0000848 - abnormal chromosome morphology during vegetative growth

References:

Genotypes:

FYPO:0001933 - abnormal mitotic cell cycle regulation during cellular response to hydroxyurea

References:

Genotypes:

FYPO:0001426 - abnormal negative regulation of mitotic DNA replication initiation resulting in partial rereplication

References:

Genotypes:

FYPO:0003165 - cut with abnormal chromosome segregation

References:

Genotypes:

FYPO:0002679 - decreased protein phosphorylation

References:

Genotypes:

FYPO:0001645 - decreased protein-protein interaction

References:

Genotypes:

FYPO:0001355 - decreased vegetative cell population growth

References:

Genotypes:

FYPO:0005773 - elongated mononucleate aseptate vegetative cell

References:

Genotypes:

FYPO:0001916 - elongated mononucleate vegetative cell

References:

Genotypes:

FYPO:0001122 - elongated vegetative cell

References:

Genotypes:

FYPO:0000402 - increased mitotic G2/M phase transition

References:

Genotypes:

FYPO:0002061 - inviable vegetative cell population

References:

Genotypes:

FYPO:0001929 - normal cell cycle regulation during cellular response to hydroxyurea

References:

Genotypes:

FYPO:0000703 - normal protein-protein interaction

References:

Genotypes:

FYPO:0001357 - normal vegetative cell population growth

References:

Genotypes:

FYPO:0000088 - sensitive to hydroxyurea

References:

Genotypes:

FYPO:0000089 - sensitive to methyl methanesulfonate

References:

Genotypes:

Protein features

PBO:0111779 - BRCT domain

Qualitative gene expression

PomGeneEx:0000020 - protein level unchanged

References:

PomGeneEx:0000013 - RNA level unchanged

References:

Quantitative gene expression

PBO:0011963 - RNA level

References:

Single locus phenotype

FYPO:0000848 - abnormal chromosome morphology during vegetative growth

References:

Genotypes:

FYPO:0001933 - abnormal mitotic cell cycle regulation during cellular response to hydroxyurea

References:

Genotypes:

FYPO:0005095 - abolished protein localization to chromatin at replication origin

References:

Genotypes:

FYPO:0002898 - abolished protein phosphorylation during cellular response to DNA damage

References:

Genotypes:

FYPO:0002471 - abolished protein phosphorylation during cellular response to ionizing radiation

References:

Genotypes:

FYPO:0000705 - abolished protein-protein interaction

References:

Genotypes:

FYPO:0004321 - altered DNA level during vegetative growth

References:

Genotypes:

FYPO:0000229 - cut

References:

Genotypes:

FYPO:0004418 - cut cell with decreased poly(A)+ mRNA export from nucleus

References:

Genotypes:

FYPO:0003165 - cut with abnormal chromosome segregation

References:

Genotypes:

FYPO:0000708 - decreased mating efficiency

References:

Genotypes:

FYPO:0003950 - decreased protein localization to chromatin at replication origin

References:

Genotypes:

FYPO:0002679 - decreased protein phosphorylation

References:

Genotypes:

FYPO:0002897 - decreased protein phosphorylation during cellular response to DNA damage

References:

Genotypes:

FYPO:0002470 - decreased protein phosphorylation during cellular response to ionizing radiation

References:

Genotypes:

FYPO:0001645 - decreased protein-protein interaction

References:

Genotypes:

FYPO:0000453 - DNA content decreased during vegetative growth

References:

Genotypes:

FYPO:0001919 - fragmented nucleus during vegetative growth

References:

Genotypes:

FYPO:0000614 - increased duration of mitotic S phase

References:

Genotypes:

FYPO:0001042 - inviable after spore germination, single or double cell division

References:

Genotypes:

FYPO:0000313 - inviable after spore germination, without cell division, with abnormal germ tube morphology

References:

Genotypes:

FYPO:0002061 - inviable vegetative cell population

References:

Genotypes:

FYPO:0003129 - loss of punctate nuclear protein localization during cellular response to ionizing radiation

References:

Genotypes:

FYPO:0001387 - loss of viability at high temperature

References:

Genotypes:

FYPO:0001927 - normal cell cycle regulation during cellular response to ionizing radiation

References:

Genotypes:

FYPO:0001164 - normal growth on glucose carbon source

References:

Genotypes:

FYPO:0004406 - normal growth on JM335

References:

Genotypes:

FYPO:0004410 - normal growth on tetraplatin

References:

Genotypes:

FYPO:0004408 - normal growth on triplatin tetranitrate

References:

Genotypes:

FYPO:0000478 - normal meiosis

References:

Genotypes:

FYPO:0004014 - normal mitotic cell cycle regulation during cellular response to UV

References:

Genotypes:

FYPO:0002043 - normal premeiotic DNA replication

References:

Genotypes:

FYPO:0003131 - normal protein phosphorylation during cellular response to ionizing radiation

References:

Genotypes:

FYPO:0000703 - normal protein-protein interaction

References:

Genotypes:

FYPO:0000943 - normal spore morphology

References:

Genotypes:

FYPO:0003130 - premature mitotic G1 phase entry during cellular response to ionizing radiation

References:

Genotypes:

FYPO:0000725 - resistance to methyl methanesulfonate

References:

Genotypes:

FYPO:0000085 - sensitive to camptothecin

References:

Genotypes:

FYPO:0000102 - sensitive to cisplatin

References:

Genotypes:

FYPO:0000266 - sensitive to DNA damaging agents

References:

Genotypes:

FYPO:0000088 - sensitive to hydroxyurea

References:

Genotypes:

FYPO:0000267 - sensitive to ionizing radiation during vegetative growth

References:

Genotypes:

FYPO:0004402 - sensitive to JM216

References:

Genotypes:

FYPO:0000089 - sensitive to methyl methanesulfonate

References:

Genotypes:

FYPO:0002345 - sensitive to oxaliplatin

References:

Genotypes:

FYPO:0000268 - sensitive to UV during vegetative growth

References:

Genotypes:

FYPO:0001234 - slow vegetative cell population growth

References:

Genotypes:

FYPO:0003612 - viable spore population

References:

Genotypes:

Taxonomic conservation

PBO:0011065 - conserved in eukaryotes

PBO:0011071 - conserved in eukaryotes only

PBO:0011064 - conserved in fungi

PBO:0011069 - conserved in metazoa

PBO:0011070 - conserved in vertebrates

PBO:0006222 - predominantly single copy (one to one)

Protein features

IDNameInterPro nameDB name
PF12738PTCB-BRCTBRCT_domPFAM
PF00533BRCTBRCT_domPFAM
cd17723BRCT_Rad4_rpt4CDD
cd18433BRCT_Rad4_rpt3CDD
cd17746BRCT_Rad4_rpt2CDD
cd17740BRCT_Rad4_rpt1CDD
PS50172BRCTBRCT_domPROSITE_PROFILES
SM00292BRCT_7BRCT_domSMART
G3DSA:3.40.50.10190:FF:000080FUNFAM
SSF52113BRCT domainBRCT_dom_sfSUPERFAMILY
G3DSA:3.40.50.10190BRCT domainBRCT_dom_sfGENE3D
PTHR13561DNA REPLICATION REGULATOR DPB11-RELATEDPANTHER

Orthologs

References / Literature

PMID:16990792 - Ordered assembly of Sld3, GINS and Cdc45 is distinctly regulated by DDK and CDK for activation of replication origins.
Yabuuchi H et al. EMBO J 2006 Oct 04;25(19):4663-74
PMID:1762905 - Cloning and characterization of the rad4 gene of Schizosaccharomyces pombe; a gene showing short regions of sequence similarity to the human XRCC1 gene.
Fenech M et al. Nucleic Acids Res 1991 Dec 25;19(24):6737-41
PMID:9739083 - Cdc18p can block mitosis by two independent mechanisms.
Greenwood E et al. J Cell Sci 1998 Oct;111 ( Pt 20):3101-8
PMID:30295604 - BRCT domains of the DNA damage checkpoint proteins TOPBP1/Rad4 display distinct specificities for phosphopeptide ligands.
Day M et al. Elife 2018 Oct 08;7
PMID:15388803 - Identification and cloning of two putative subunits of DNA polymerase epsilon in fission yeast.
Spiga MG et al. Nucleic Acids Res 2004;32(16):4945-53
GO_REF:0000033 - Annotation inferences using phylogenetic trees
PMID:24663817 - Rad4 mainly functions in Chk1-mediated DNA damage checkpoint pathway as a scaffold protein in the fission yeast Schizosaccharomyces pombe.
Yue M et al. PLoS One 2014;9(3):e92936
PMID:2004701 - A gene in Schizosaccharomyces pombe analogous to the RAD4 gene of Saccharomyces cerevisiae.
Choi IS et al. FEMS Microbiol Lett 1991 Jan 01;61(1):97-100
PMID:22761595 - The Rad4(TopBP1) ATR-activation domain functions in G1/S phase in a chromatin-dependent manner.
Lin SJ et al. PLoS Genet 2012 Jun;8(6):e1002801
PMID:23101633 - Quantitative analysis of fission yeast transcriptomes and proteomes in proliferating and quiescent cells.
Marguerat S et al. Cell 2012 Oct 26;151(3):671-83
PMID:24074952 - Phosphorylation-dependent assembly and coordination of the DNA damage checkpoint apparatus by Rad4(TopBP1).
Qu M et al. Mol Cell 2013 Sep 26;51(6):723-736
PMID:27984725 - CDK Substrate Phosphorylation and Ordering the Cell Cycle.
Swaffer MP et al. Cell 2016 Dec 15;167(7):1750-1761.e16
PMID:30726745 - Fission Yeast NDR/LATS Kinase Orb6 Regulates Exocytosis via Phosphorylation of the Exocyst Complex.
Tay YD et al. Cell Rep 2019 Feb 05;26(6):1654-1667.e7
PMID:11027263 - Schizosaccharomyces pombe Hsk1p is a potential cds1p target required for genome integrity.
Snaith HA et al. Mol Cell Biol 2000 Nov;20(21):7922-32
PMID:7254221 - Spontaneous and UV-induced recombination in radiation-sensitive mutants of Schizosaccharomyces pombe.
Grossenbacher-Grunder AM et al. Mutat Res 1981 Mar;81(1):37-48
PMID:11606526 - Characterization of Schizosaccharomyces pombe mcm7(+) and cdc23(+) (MCM10) and interactions with replication checkpoints.
Liang DT et al. Genetics 2001 Oct;159(2):471-86
PMID:15161942 - The nucleolus is involved in mRNA export from the nucleus in fission yeast.
Ideue T et al. J Cell Sci 2004 Jun 15;117(Pt 14):2887-95
PMID:20118936 - Schizosaccharomyces pombe genome-wide nucleosome mapping reveals positioning mechanisms distinct from those of Saccharomyces cerevisiae.
Lantermann AB et al. Nat Struct Mol Biol 2010 Feb;17(2):251-7
PMID:9268024 - Characterisation of the Schizosaccharomyces pombe rad4/cut5 mutant phenotypes: dissection of DNA replication and G2 checkpoint control function.
McFarlane RJ et al. Mol Gen Genet 1997 Jul;255(3):332-40
PMID:15466421 - A screen for Schizosaccharomyces pombe mutants defective in rereplication identifies new alleles of rad4+, cut9+ and psf2+.
Gómez EB et al. Genetics 2005 Jan;169(1):77-89
PMID:12865439 - Delineating the position of rad4+/cut5+ within the DNA-structure checkpoint pathways in Schizosaccharomyces pombe.
Harris S et al. J Cell Sci 2003 Sep 01;116(Pt 17):3519-29
PMID:21593208 - CDK promotes interactions of Sld3 and Drc1 with Cut5 for initiation of DNA replication in fission yeast.
Fukuura M et al. Mol Biol Cell 2011 Jul 15;22(14):2620-33
PMID:33823663 - A TOR (target of rapamycin) and nutritional phosphoproteome of fission yeast reveals novel targets in networks conserved in humans.
Halova L et al. Open Biol 2021 Apr;11(4):200405
PMID:10888871 - Mitotic replication initiation proteins are not required for pre-meiotic S phase.
Forsburg SL et al. Nat Genet 2000 Jul;25(3):263-8
PMID:10388806 - Rereplication phenomenon in fission yeast requires MCM proteins and other S phase genes.
Snaith HA et al. Genetics 1999 Jul;152(3):839-51
PMID:1563349 - Checkpoint controls in Schizosaccharomyces pombe: rad1.
Rowley R et al. EMBO J 1992 Apr;11(4):1335-42
PMID:21945095 - Mcm10 interacts with Rad4/Cut5(TopBP1) and its association with origins of DNA replication is dependent on Rad4/Cut5(TopBP1).
Taylor M et al. DNA Repair (Amst) 2011 Nov 10;10(11):1154-63
PMID:23322785 - The fission yeast minichromosome maintenance (MCM)-binding protein (MCM-BP), Mcb1, regulates MCM function during prereplicative complex formation in DNA replication.
Santosa V et al. J Biol Chem 2013 Mar 08;288(10):6864-80
PMID:39367033 - Quantitative proteomics and phosphoproteomics profiling of meiotic divisions in the fission yeast Schizosaccharomyces pombe.
Sivakova B et al. Sci Rep 2024 Oct 04;14(1):23105
PMID:8846774 - Fission yeast rad17: a homologue of budding yeast RAD24 that shares regions of sequence similarity with DNA polymerase accessory proteins.
Griffiths DJ et al. EMBO J 1995 Dec 01;14(23):5812-23
PMID:17112379 - The CENP-B homolog, Abp1, interacts with the initiation protein Cdc23 (MCM10) and is required for efficient DNA replication in fission yeast.
Locovei AM et al. Cell Div 2006 Nov 17;1:27
PMID:166019 - Genetic control of radiation sensitivity in Schizosaccharomyces pombe.
Nasim A et al. Genetics 1975 Apr;79(4):573-82
PMID:22433840 - Mcm10 plays an essential role in origin DNA unwinding after loading of the CMG components.
Kanke M et al. EMBO J 2012 May 02;31(9):2182-94
PMID:29996109 - Quantitative Phosphoproteomics Reveals the Signaling Dynamics of Cell-Cycle Kinases in the Fission Yeast Schizosaccharomyces pombe.
Swaffer MP et al. Cell Rep 2018 Jul 10;24(2):503-514
PMID:7957098 - Fission yeast cut5 links nuclear chromatin and M phase regulator in the replication checkpoint control.
Saka Y et al. EMBO J 1994 Nov 15;13(22):5319-29
PMID:16453724 - Isolation and characterization of Schizosaccharomyces pombe cutmutants that block nuclear division but not cytokinesis.
Hirano T et al. EMBO J 1986 Nov;5(11):2973-9
PMID:22681890 - Hierarchical modularity and the evolution of genetic interactomes across species.
Ryan CJ et al. Mol Cell 2012 Jun 08;46(5):691-704
PMID:32372157 - Characterisation of unessential genes required for survival under conditions of DNA stress.
Ahmed Ezzat H et al. J Genet Eng Biotechnol 2020 May 06;18(1):14
PMID:27298342 - Identification of S-phase DNA damage-response targets in fission yeast reveals conservation of damage-response networks.
Willis NA et al. Proc Natl Acad Sci U S A 2016 Jun 28;113(26):E3676-85
PMID:977546 - Temperature-sensitive mutant of Schizosaccharomyces pombe exhibiting enhanced radiation sensitivity.
Duck P et al. J Bacteriol 1976 Nov;128(2):536-9
PMID:23628481 - A proteome-wide visual screen identifies fission yeast proteins localizing to DNA double-strand breaks.
Yu Y et al. DNA Repair (Amst) 2013 Jun 01;12(6):433-43
PMID:9894912 - Cut5 is a component of the UV-responsive DNA damage checkpoint in fission yeast.
Verkade HM et al. Mol Gen Genet 1998 Dec;260(5):426-33
PMID:20473289 - Analysis of a genome-wide set of gene deletions in the fission yeast Schizosaccharomyces pombe.
Kim DU et al. Nat Biotechnol 2010 Jun;28(6):617-623
PMID:14739927 - Regulation of checkpoint kinases through dynamic interaction with Crb2.
Mochida S et al. EMBO J 2004 Jan 28;23(2):418-28
PMID:16823372 - ORFeome cloning and global analysis of protein localization in the fission yeast Schizosaccharomyces pombe.
Matsuyama A et al. Nat Biotechnol 2006 Jul;24(7):841-7
PMID:31719112 - Checkpoint Regulation of Nuclear Tos4 Defines S Phase Arrest in Fission Yeast.
Kim SM et al. G3 (Bethesda) 2020 Jan 07;10(1):255-266
PMID:16778077 - Histone modification-dependent and -independent pathways for recruitment of checkpoint protein Crb2 to double-strand breaks.
Du LL et al. Genes Dev 2006 Jun 15;20(12):1583-96
PMID:16723501 - Rad4TopBP1, a scaffold protein, plays separate roles in DNA damage and replication checkpoints and DNA replication.
Taricani L et al. Mol Biol Cell 2006 Aug;17(8):3456-68
PMID:25720772 - Quantitative phosphoproteomics reveals pathways for coordination of cell growth and division by the conserved fission yeast kinase pom1.
Kettenbach AN et al. Mol Cell Proteomics 2015 May;14(5):1275-87
PMID:21511999 - Comparative functional genomics of the fission yeasts.
Rhind N et al. Science 2011 May 20;332(6032):930-6
PMID:17272281 - Rad4TopBP1 associates with Srr2, an Spc1 MAPK-regulated protein, in response to environmental stress.
Taricani L et al. J Biol Chem 2007 Mar 23;282(12):8793-800
PMID:22792081 - Phosphorylation-dependent interactions between Crb2 and Chk1 are essential for DNA damage checkpoint.
Qu M et al. PLoS Genet 2012 Jul;8(7):e1002817
PMID:22718908 - DNA polymerization-independent functions of DNA polymerase epsilon in assembly and progression of the replisome in fission yeast.
Handa T et al. Mol Biol Cell 2012 Aug;23(16):3240-53
PMID:21095590 - DDK phosphorylates checkpoint clamp component Rad9 and promotes its release from damaged chromatin.
Furuya K et al. Mol Cell 2010 Nov 24;40(4):606-18
PMID:9407031 - Damage and replication checkpoint control in fission yeast is ensured by interactions of Crb2, a protein with BRCT motif, with Cut5 and Chk1.
Saka Y et al. Genes Dev 1997 Dec 15;11(24):3387-400
PMID:11523776 - Sna41goa1, a novel mutation causing G1/S arrest in fission yeast, is defective in a CDC45 homolog and interacts genetically with polalpha.
Uchiyama M et al. Mol Genet Genomics 2001 Aug;265(6):1039-49
PMID:19547744 - Evolution of phosphoregulation: comparison of phosphorylation patterns across yeast species.
Beltrao P et al. PLoS Biol 2009 Jun 16;7(6):e1000134
PMID:8395535 - Identification of seven new cut genes involved in Schizosaccharomyces pombe mitosis.
Samejima I et al. J Cell Sci 1993 May;105 ( Pt 1):135-43
PMID:15155581 - Chk1 activation requires Rad9 S/TQ-site phosphorylation to promote association with C-terminal BRCT domains of Rad4TOPBP1.
Furuya K et al. Genes Dev 2004 May 15;18(10):1154-64
PMID:37970674 - SUMOylation regulates Lem2 function in centromere clustering and silencing.
Strachan J et al. J Cell Sci 2023 Dec 01;136(23)
PMID:9658208 - Sensitivity to cisplatin and platinum-containing compounds of Schizosaccharomyces pombe rad mutants.
Perego P et al. Mol Pharmacol 1998 Jul;54(1):213-9
PMID:8290359 - Cloning and characterisation of the Schizosaccharomyces pombe rad8 gene, a member of the SNF2 helicase family.
Doe CL et al. Nucleic Acids Res 1993 Dec 25;21(25):5964-71
PMID:8343962 - Fission yeast cut5+, required for S phase onset and M phase restraint, is identical to the radiation-damage repair gene rad4+.
Saka Y et al. Cell 1993 Jul 30;74(2):383-93
PMID:23697806 - A genome-wide resource of cell cycle and cell shape genes of fission yeast.
Hayles J et al. Open Biol 2013 May 22;3(5):130053
PMID:11937031 - CDK phosphorylation of Drc1 regulates DNA replication in fission yeast.
Noguchi E et al. Curr Biol 2002 Apr 02;12(7):599-605
PMID:9488484 - Isolation, characterization, and molecular cloning of a protein (Abp2) that binds to a Schizosaccharomyces pombe origin of replication (ars3002).
Sanchez JP et al. Mol Cell Biol 1998 Mar;18(3):1670-81
PMID:15229228 - Homo-oligomerization is the essential function of the tandem BRCT domains in the checkpoint protein Crb2.
Du LL et al. J Biol Chem 2004 Sep 10;279(37):38409-14
PMID:14718568 - TopBP1 and ATR colocalization at meiotic chromosomes: role of TopBP1/Cut5 in the meiotic recombination checkpoint.
Perera D et al. Mol Biol Cell 2004 Apr;15(4):1568-79