protein coding gene - crb2 (SPBC342.05) - BRCT and tudor domain DNA checkpoint protein Crb2

Gene summary

Standard name

crb2

Systematic ID

SPBC342.05

Product

BRCT and tudor domain DNA checkpoint protein Crb2

Organism

Schizosaccharomyces pombe (fission yeast)

Synonyms

rhp9

UniProt ID

P87074

ORFeome ID

33/33G08

Characterisation status

biological role published

Feature type

mRNA gene

Genomic location

chromosome II: 4210967..4213577 forward strand

Annotation

Protein features

Orthologs

• TP53BP1 (HGNC:11999) Homo sapiens
• crb2 (SJAG_01205) Schizosaccharomyces japonicus
• RAD9 (YDR217C) Saccharomyces cerevisiae

References / Literature

PMID:29697047 - Rev7 and 53BP1/Crb2 prevent RecQ helicase-dependent hyper-resection of DNA double-strand breaks.

Leland BA et al. Elife 2018 Apr 26;7

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:12023299 - Cdc2-cyclin B kinase activity links Crb2 and Rqh1-topoisomerase III.

Caspari T et al. Genes Dev 2002 May 15;16(10):1195-208

PMID:26771498 - A Proteome-wide Fission Yeast Interactome Reveals Network Evolution Principles from Yeasts to Human.

Vo TV et al. Cell 2016 Jan 14;164(1-2):310-323

PMID:14655046 - Two-hybrid search for proteins that interact with Sad1 and Kms1, two membrane-bound components of the spindle pole body in fission yeast.

Miki F et al. Mol Genet Genomics 2004 Jan;270(6):449-61

PMID:23173672 - Identification of novel genes involved in DNA damage response by screening a genome-wide Schizosaccharomyces pombe deletion library.

Pan X et al. BMC Genomics 2012 Nov 23;13:662

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:16816416 - Antagonism of Chk1 signaling in the G2 DNA damage checkpoint by dominant alleles of Cdr1.

Calonge TM et al. Genetics 2006 Sep;174(1):113-23

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:12196391 - Telomere binding of checkpoint sensor and DNA repair proteins contributes to maintenance of functional fission yeast telomeres.

Nakamura TM et al. Genetics 2002 Aug;161(4):1437-52

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:21098122 - Mre11 nuclease activity and Ctp1 regulate Chk1 activation by Rad3ATR and Tel1ATM checkpoint kinases at double-strand breaks.

Limbo O et al. Mol Cell Biol 2011 Feb;31(3):573-83

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:10521402 - Meiotic DNA replication checkpoint control in fission yeast.

Murakami H et al. Genes Dev 1999 Oct 01;13(19):2581-93

PMID:11226171 - Novel functional requirements for non-homologous DNA end joining in Schizosaccharomyces pombe.

Manolis KG et al. EMBO J 2001 Jan 15;20(1-2):210-21

PMID:16314498 - Cooperative control of Crb2 by ATM family and Cdc2 kinases is essential for the DNA damage checkpoint in fission yeast.

Nakamura TM et al. Mol Cell Biol 2005 Dec;25(24):10721-30

PMID:39476757 - Characterization of Ksg1 protein kinase-dependent phosphoproteome in the fission yeast S. pombe.

Cipak L et al. Biochem Biophys Res Commun 2024 Oct 25;736:150895

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:14560029 - Swi1 prevents replication fork collapse and controls checkpoint kinase Cds1.

Noguchi E et al. Mol Cell Biol 2003 Nov;23(21):7861-74

PMID:9928931 - The S/M checkpoint at 37 degrees C and the recovery of viability of the mutant poldeltats3 require the crb2+/rhp9+ gene in fission yeast.

Grenon M et al. Mol Gen Genet 1999 Jan;260(6):522-34

PMID:22645654 - Opposing role of condensin hinge against replication protein A in mitosis and interphase through promoting DNA annealing.

Akai Y et al. Open Biol 2011 Dec;1(4):110023

PMID:17190600 - Structural basis for the methylation state-specific recognition of histone H4-K20 by 53BP1 and Crb2 in DNA repair.

Botuyan MV et al. Cell 2006 Dec 29;127(7):1361-73

PMID:24763107 - Absolute proteome and phosphoproteome dynamics during the cell cycle of Schizosaccharomyces pombe (Fission Yeast).

Carpy A et al. Mol Cell Proteomics 2014 Aug;13(8):1925-36

PMID:19264558 - Screening a genome-wide S. pombe deletion library identifies novel genes and pathways involved in genome stability maintenance.

Deshpande GP et al. DNA Repair (Amst) 2009 May 01;8(5):672-9

PMID:24861625 - Hyperactive Cdc2 kinase interferes with the response to broken replication forks by trapping S.pombe Crb2 in its mitotic T215 phosphorylated state.

Mahyous Saeyd SA et al. Nucleic Acids Res 2014 Jul;42(12):7734-47

PMID:28410370 - A systematic screen for morphological abnormalities during fission yeast sexual reproduction identifies a mechanism of actin aster formation for cell fusion.

Dudin O et al. PLoS Genet 2017 Apr;13(4):e1006721

PMID:31332096 - A tel2 Mutation That Destabilizes the Tel2-Tti1-Tti2 Complex Eliminates Rad3 ATR Kinase Signaling in the DNA Replication Checkpoint and Leads to Telomere Shortening in Fission Yeast.

Xu YJ et al. Mol Cell Biol 2019 Oct 15;39(20)

PMID:31542296 - Rad52 Restrains Resection at DNA Double-Strand Break Ends in Yeast.

Yan Z et al. Mol Cell 2019 Dec 05;76(5):699-711.e6

PMID:21712547 - Mitotic substrates of the kinase aurora with roles in chromatin regulation identified through quantitative phosphoproteomics of fission yeast.

Koch A et al. Sci Signal 2011 Jun 28;4(179):rs6

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:30148840 - Tdp1 processes chromate-induced single-strand DNA breaks that collapse replication forks.

Ganguly A et al. PLoS Genet 2018 Aug;14(8):e1007595

PMID:15329725 - Separase-mediated cleavage of cohesin at interphase is required for DNA repair.

Nagao K et al. Nature 2004 Aug 26;430(7003):1044-8

PMID:18676809 - Structural and functional analysis of the Crb2-BRCT2 domain reveals distinct roles in checkpoint signaling and DNA damage repair.

Kilkenny ML et al. Genes Dev 2008 Aug 01;22(15):2034-47

PMID:18344406 - Schizosaccharomyces pombe Hst4 functions in DNA damage response by regulating histone H3 K56 acetylation.

Haldar D et al. Eukaryot Cell 2008 May;7(5):800-13

PMID:24806815 - Mdb1, a fission yeast homolog of human MDC1, modulates DNA damage response and mitotic spindle function.

Wei Y et al. PLoS One 2014;9(5):e97028

PMID:12000964 - Cnd2 has dual roles in mitotic condensation and interphase.

Aono N et al. Nature 2002 May 09;417(6885):197-202

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:22907753 - Posttranscriptional regulation of cell-cell interaction protein-encoding transcripts by Zfs1p in Schizosaccharomyces pombe.

Wells ML et al. Mol Cell Biol 2012 Oct;32(20):4206-14

PMID:15550243 - Methylation of histone H4 lysine 20 controls recruitment of Crb2 to sites of DNA damage.

Sanders SL et al. Cell 2004 Nov 24;119(5):603-14

PMID:16371652 - Production of reactive oxygen species in response to replication stress and inappropriate mitosis in fission yeast.

Marchetti MA et al. J Cell Sci 2006 Jan 01;119(Pt 1):124-31

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:12081644 - Fission yeast chk1 mutants show distinct responses to different types of DNA damaging treatments.

Francesconi S et al. Genes Cells 2002 Jul;7(7):663-73

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:22095079 - The double-bromodomain proteins Bdf1 and Bdf2 modulate chromatin structure to regulate S-phase stress response in Schizosaccharomyces pombe.

Garabedian MV et al. Genetics 2012 Feb;190(2):487-500

PMID:11809834 - Fission yeast F-box protein Pof3 is required for genome integrity and telomere function.

Katayama S et al. Mol Biol Cell 2002 Jan;13(1):211-24

PMID:18818364 - Conservation and rewiring of functional modules revealed by an epistasis map in fission yeast.

Roguev A et al. Science 2008 Oct 17;322(5900):405-10

PMID:29084823 - Phosphorylation of the RNA-binding protein Zfs1 modulates sexual differentiation in fission yeast.

Navarro FJ et al. J Cell Sci 2017 Dec 15;130(24):4144-4154

PMID:21511999 - Comparative functional genomics of the fission yeasts.

Rhind N et al. Science 2011 May 20;332(6032):930-6

PMID:37787768 - Broad functional profiling of fission yeast proteins using phenomics and machine learning.

Rodríguez-López M et al. Elife 2023 Oct 03;12

PMID:18931302 - Significant conservation of synthetic lethal genetic interaction networks between distantly related eukaryotes.

Dixon SJ et al. Proc Natl Acad Sci U S A 2008 Oct 28;105(43):16653-8

PMID:19205745 - Redundant roles of Srs2 helicase and replication checkpoint in survival and rDNA maintenance in Schizosaccharomyces pombe.

Yasuhira S Mol Genet Genomics 2009 May;281(5):497-509

PMID:12832769 - Expression, purification and preliminary X-ray analysis of the BRCT domain from Rhp9/Crb2.

Hinks JA et al. Acta Crystallogr D Biol Crystallogr 2003 Jul;59(Pt 7):1230-3

PMID:18378696 - Molecular characterization of the role of the Schizosaccharomyces pombe nip1+/ctp1+ gene in DNA double-strand break repair in association with the Mre11-Rad50-Nbs1 complex.

Akamatsu Y et al. Mol Cell Biol 2008 Jun;28(11):3639-51

PMID:20094029 - gammaH2A binds Brc1 to maintain genome integrity during S-phase.

Williams JS et al. EMBO J 2010 Mar 17;29(6):1136-48

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:22737087 - The CCR4-NOT complex is implicated in the viability of aneuploid yeasts.

Tange Y et al. PLoS Genet 2012;8(6):e1002776

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:20176980 - Fission yeast Hsk1 (Cdc7) kinase is required after replication initiation for induced mutagenesis and proper response to DNA alkylation damage.

Dolan WP et al. Genetics 2010 May;185(1):39-53

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:15226425 - Histone H2A phosphorylation controls Crb2 recruitment at DNA breaks, maintains checkpoint arrest, and influences DNA repair in fission yeast.

Nakamura TM et al. Mol Cell Biol 2004 Jul;24(14):6215-30

PMID:23695164 - Cross-species protein interactome mapping reveals species-specific wiring of stress response pathways.

Das J et al. Sci Signal 2013 May 21;6(276):ra38

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:15498101 - Germinating fission yeast spores delay in G1 in response to UV irradiation.

Nilssen EA et al. BMC Cell Biol 2004 Oct 21;5(1):40

PMID:11715016 - Mrc1 transduces signals of DNA replication stress to activate Rad53.

Alcasabas AA et al. Nat Cell Biol 2001 Nov;3(11):958-65

PMID:26368543 - Critical Function of γH2A in S-Phase.

Mejia-Ramirez E et al. PLoS Genet 2015 Sep;11(9):e1005517

PMID:9153313 - Isolation and characterization of the Schizosaccharomyces pombe rhp9 gene: a gene required for the DNA damage checkpoint but not the replication checkpoint.

Willson J et al. Nucleic Acids Res 1997 Jun 01;25(11):2138-46

PMID:17690116 - Cdc18/CDC6 activates the Rad3-dependent checkpoint in the fission yeast.

Fersht N et al. Nucleic Acids Res 2007;35(16):5323-37

PMID:18826944 - Di-methyl H4 lysine 20 targets the checkpoint protein Crb2 to sites of DNA damage.

Greeson NT et al. J Biol Chem 2008 Nov 28;283(48):33168-74

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:25417108 - Dicer promotes transcription termination at sites of replication stress to maintain genome stability.

Castel SE et al. Cell 2014 Oct 23;159(3):572-83

PMID:10757807 - Cid1, a fission yeast protein required for S-M checkpoint control when DNA polymerase delta or epsilon is inactivated.

Wang SW et al. Mol Cell Biol 2000 May;20(9):3234-44

PMID:12930957 - Nuclear factories for signalling and repairing DNA double strand breaks in living fission yeast.

Meister P et al. Nucleic Acids Res 2003 Sep 01;31(17):5064-73

PMID:25795664 - Genetic Interaction Landscape Reveals Critical Requirements for Schizosaccharomyces pombe Brc1 in DNA Damage Response Mutants.

Sánchez A et al. G3 (Bethesda) 2015 Mar 19;5(5):953-62

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:20537132 - Global fitness profiling of fission yeast deletion strains by barcode sequencing.

Han TX et al. Genome Biol 2010;11(6):R60

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:20679488 - Requirement for the phospho-H2AX binding module of Crb2 in double-strand break targeting and checkpoint activation.

Sanders SL et al. Mol Cell Biol 2010 Oct;30(19):4722-31

PMID:12839619 - High dosage Rhp51 suppression of the MMS sensitivity of DNA structure checkpoint mutants reveals a relationship between Crb2 and Rhp51.

Smeets MF et al. Genes Cells 2003 Jul;8(7):573-86

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:18667534 - Activation of the DNA damage checkpoint in mutants defective in DNA replication initiation.

Yin L et al. Mol Biol Cell 2008 Oct;19(10):4374-82

PMID:33723569 - Schizosaccharomyces pombe KAT5 contributes to resection and repair of a DNA double-strand break.

Li T et al. Genetics 2021 May 17;218(1)

PMID:23188080 - The fission yeast MRN complex tethers dysfunctional telomeres for NHEJ repair.

Reis CC et al. EMBO J 2012 Dec 12;31(24):4576-86

PMID:10488332 - Cdc2 phosphorylation of Crb2 is required for reestablishing cell cycle progression after the damage checkpoint.

Esashi F et al. Mol Cell 1999 Aug;4(2):167-74

PMID:10648611 - Characterization of Schizosaccharomyces pombe Hus1: a PCNA-related protein that associates with Rad1 and Rad9.

Caspari T et al. Mol Cell Biol 2000 Feb;20(4):1254-62

PMID:20679485 - BRCT domain interactions with phospho-histone H2A target Crb2 to chromatin at double-strand breaks and maintain the DNA damage checkpoint.

Sofueva S et al. Mol Cell Biol 2010 Oct;30(19):4732-43

PMID:17936710 - Ctp1 is a cell-cycle-regulated protein that functions with Mre11 complex to control double-strand break repair by homologous recombination.

Limbo O et al. Mol Cell 2007 Oct 12;28(1):134-46

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: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:27098497 - CRL4(Wdr70) regulates H2B monoubiquitination and facilitates Exo1-dependent resection.

Zeng M et al. Nat Commun 2016 Apr 21;7:11364

PMID:12589755 - The fission yeast spSet1p is a histone H3-K4 methyltransferase that functions in telomere maintenance and DNA repair in an ATM kinase Rad3-dependent pathway.

Kanoh J et al. J Mol Biol 2003 Feb 28;326(4):1081-94

PMID:19250904 - Regulation of Set9-mediated H4K20 methylation by a PWWP domain protein.

Wang Y et al. Mol Cell 2009 Feb 27;33(4):428-37

PMID:21561865 - The phosphorylation network for efficient activation of the DNA replication checkpoint in fission yeast.

Yue M et al. J Biol Chem 2011 Jul 01;286(26):22864-74

PMID:18257517 - Phosphoproteome analysis of fission yeast.

Wilson-Grady JT et al. J Proteome Res 2008 Mar;7(3):1088-97

PMID:23422000 - Regulatory motifs in Chk1.

Caparelli ML et al. Cell Cycle 2013 Mar 15;12(6):916-22

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:10373582 - The role of Schizosaccharomyces pombe Rad32, the Mre11 homologue, and other DNA damage response proteins in non-homologous end joining and telomere length maintenance.

Wilson S et al. Nucleic Acids Res 1999 Jul 01;27(13):2655-61