Search results for ERCC1

Showing 17 results out of 28

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Protein (2 results from a total of 2)

Identifier: R-HSA-54427
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: ERCC1: P07992
Identifier: R-HSA-5696473
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: ERCC1: P07992

Interactor (1 results from a total of 1)

Identifier: P07992-3
Species: Homo sapiens
Primary external reference: UniProt: P07992-3

Reaction (6 results from a total of 17)

Identifier: R-HSA-5696465
Species: Homo sapiens
Compartment: nucleoplasm
USP45 ubiquitin protease, mutated in prostate cancer and B-cell lymphoma, deubiquitinates ERCC1. While the mechanism and timing of ERCC1 ubiquitination are not known, deubiquitination of ERCC1 by USP45 enables ERCC1 recruitment to DNA damage sites in nucleotide excision repair (NER) and repair of interstrand cross-links (ICLR) (Perez-Oliva et al. 2015).
Identifier: R-HSA-6782141
Species: Homo sapiens
Compartment: nucleoplasm
ERCC1:ERCC4 (ERCC1:XPF) DNA endonuclease complex binds to the pre-incision complex at the transcription-coupled nucleotide excision repair (TC-NER) site to form the incision complex. Binding of ERCC5 (XPG) to the NER site precedes the recruitment of ERCC1:ERCC4 (Riedl et al. 2003). ERCC1 directly interacts with the XPA, and this interaction is necessary for the loading of ERCC1:ERCC4 to the open bubble structure in damaged dsDNA and the progression of TC-NER (Tsodikov et al. 2007, Orelli et al. 2010).
Identifier: R-HSA-5690991
Species: Homo sapiens
Compartment: nucleoplasm
ERCC1:ERCC4 (ERCC1:XPF) DNA endonuclease complex binds 5' to the DNA damage at global genome nucleotide excision repair (GG-NER) sites to form the incision complex. Binding of ERCC5 (XPG) to the NER site precedes the recruitment of ERCC1:ERCC4 (Riedl et al. 2003). ERCC1 directly interacts with XPA, and this interaction is necessary for the loading of ERCC1:ERCC4 to the open bubble structure in damaged dsDNA and the progression of GG-NER (Tsodikov et al. 2007, Orelli et al. 2010).
Identifier: R-HSA-109955
Species: Homo sapiens
Compartment: nucleoplasm
ERCC1 binds ERCC4 (XPF) to form a heterodimeric ERCC1:ERCC4 (ERCC1:XPF) complex with a DNA endonuclease activity, where ERCC4 is the catalytic subunit. Suitable substrates for the ERCC1:ERCC4 endonuclease are single strand DNA (ssDNA) and ssDNA region of a duplex DNA with an open bubble structure (Park et al. 1995).
Identifier: R-HSA-5686657
Species: Homo sapiens
Compartment: nucleoplasm
The endonuclease complex ERCC1:XPF (ERCC1:ERCC4) is recruited to single strand annealing (SSA) sites of DNA double strand break (DSB) repair through direct interaction between XPF (ERCC4) and RAD52 (Motycka et al. 2004). ERCC1:XPF cleaves the ssDNA flaps generated by displacement of non-complementary 3' parts of 3' ssDNA overhangs during RAD52-mediated annealing. The enzymatic activity of ERCC1:XPF is necessary for the completion of SSA (Motycka et al. 2004, Al-Minawi et al. 2008, Ahmad et al. 2008).
Identifier: R-HSA-5690990
Species: Homo sapiens
Compartment: nucleoplasm
In global genome nucleotide excision repair (GG-NER), just like in transcription-coupled nucleotide excision repair (TC-NER), the cleavage of the damaged strand of DNA 5' to the site of damage occurs at the junction of single-stranded DNA and double-stranded DNA that is formed when the DNA duplex is unwound. The 5' incision is carried out by the ERCC1:XPF (ERCC1:ERCC4) complex and precedes the 3' incision (Staresincic et al. 2009).

Complex (2 results from a total of 2)

Identifier: R-HSA-109943
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-6782142
Species: Homo sapiens
Compartment: nucleoplasm

Pathway (6 results from a total of 6)

Identifier: R-HSA-5696395
Species: Homo sapiens
Compartment: nucleoplasm
After the XPC complex and the UV-DDB complex bind damaged DNA, a basal transcription factor TFIIH is recruited to the nucleotide excision repair (NER) site (Volker et al. 2001, Riedl et al. 2003). DNA helicases ERCC2 (XPD) and ERCC3 (XPB) are subunits of the TFIIH complex. ERCC2 unwinds the DNA around the damage in concert with the ATPase activity of ERCC3, creating an open bubble (Coin et al. 2007). Simultaneously, the presence of the damage is verified by XPA (Camenisch et al. 2006). The recruitment of XPA is partially regulated by PARP1 and/or PARP2 (King et al. 2012).

Two DNA endonucleases, ERCC5 (XPG) and the complex of ERCC1 and ERCC4 (XPF), are recruited to the open bubble structure to form the incision complex that will excise the damaged oligonucleotide from the affected DNA strand (Dunand-Sauthier et al. 2005, Zotter et al. 2006, Riedl et al. 2003, Tsodikov et al. 2007, Orelli et al. 2010). The RPA heterotrimer coats the undamaged DNA strand, thus protecting it from the endonucleolytic attack (De Laat et al. 1998).

Identifier: R-HSA-5685938
Species: Homo sapiens
Homology directed repair (HDR) through single strand annealing (SSA), similar to HDR through homologous recombination repair (HRR), involves extensive resection of DNA double strand break ends (DSBs), preceded by ATM activation and formation of the so-called ionizing radiation induced foci (IRIF) at DNA DSB sites. Following ATM activation and foci formation, the two-step resection is initiated by the MRN complex (MRE11A:RAD50:NBN) and RBBP8 (CtIP) associated with BRCA1:BARD1, and completed by EXO1 or DNA2 in cooperation with DNA helicases BLM, WRN and BRIP1 (BACH1) (Sartori et al. 2007, Yun and Hiom 2009, Eid et al. 2010, Nimonkar et al. 2011, Suhasini et al. 2011, Sturzenegger et al. 2014). Long 3'-ssDNA overhangs produced by extensive resection are coated by the RPA heterotrimer (RPA1:RPA2:RPA3), triggering ATR signaling. ATR signaling is needed for SSA, probably because of the related phosphorylation of RPA2 (Zou and Elledge 2003, Anantha et al. 2007, Liu et al. 2012).

RAD52 is the key mediator of SSA. Activated ATM phosphorylates and activates ABL1, and activated ABL1 subsequently phosphorylates pre-formed RAD52 heptameric rings, increasing their affinity for ssDNA (Honda et al. 2011). Phosphorylated RAD52 binds phosphorylated RPA heterotrimers on 3'-ssDNA overhangs at resected DNA DSBs. RAD52 also binds RAD51 and prevents formation of invasive RAD51 nucleofilaments involved in HRR (Chen et al. 1999, Van Dyck et al. 1999, Parsons et al. 2000, Jackson et al. 2002, Singleton et al. 2002).

RAD52 promotes annealing of two 3'-ssDNA overhangs when highly homologous directed repeats are present in both 3'-ssDNA overhangs. Nonhomologous regions lying 3' to the annealed repeats are displaced as 3'-flaps (Parsons et al. 2000, Van Dyck et al. 2001, Singleton et al. 2002, Stark et al. 2004, Mansour et al. 2008). The endonuclease complex composed of ERCC1 and ERCC4 (XPF) is subsequently recruited to SSA sites through direct interaction between RAD52 and ERCC4, leading to cleavage of 3' flaps (Motycka et al. 2004, Al-Minawi et al. 2008). The identity of a DNA ligase that closes the remaining single strand nicks (SSBs) to complete SSA-mediated repair is not known.

SSA results in deletion of one of the annealed repeats and the intervening DNA sequence between the two annealed repeats and is thus mutagenic.

Identifier: R-HSA-5696400
Species: Homo sapiens
Compartment: nucleoplasm
Double incision at the damaged DNA strand excises the oligonucleotide that contains the lesion from the open bubble. The excised oligonucleotide is ~27-30 bases long. Incision 5' to the damage site, by ERCC1:ERCC4 endonuclease, precedes the incision 3' to the damage site by ERCC5 endonuclease (Staresincic et al. 2009).
Identifier: R-HSA-6782135
Species: Homo sapiens
Compartment: nucleoplasm
In transcription-coupled nucleotide excision repair (TC-NER), similar to global genome nucleotide excision repair (GG-NER), the oligonucleotide that contains the lesion is excised from the open bubble structure via dual incision of the affected DNA strand. 5' incision by the ERCC1:ERCC4 (ERCC1:XPF) endonuclease precedes 3' incision by ERCC5 (XPG) endonuclease. In order for the TC-NER pre-incision complex to assemble and the endonucleases to incise the damaged DNA strand, the RNA polymerase II (RNA Pol II) complex has to backtrack - reverse translocate from the damage site. Although the mechanistic details of this process are largely unknown in mammals, it may involve ERCC6/ERCC8-mediated chromatin remodelling/ubiquitination events, the DNA helicase activity of the TFIIH complex and TCEA1 (TFIIS)-stimulated cleavage of the 3' protruding end of nascent mRNA by RNA Pol II (Donahue et al. 1994, Lee et al. 2002, Sarker et al. 2005, Vermeulen and Fousteri 2013, Hanawalt and Spivak 2008, Staresincic et al. 2009, Epshtein et al. 2014).
Identifier: R-HSA-5696399
Species: Homo sapiens
Compartment: nucleoplasm
The DNA damage in GG-NER is recognized by the joint action of two protein complexes. The first complex is composed of XPC, RAD23A or RAD23B and CETN2. The second complex, known as the UV-DDB complex, is an ubiquitin ligase composed of DDB1, CUL4A or CUL4B, RBX1 and a GG-NER specific protein DDB2. In vitro, the UV-DDB complex is onlynecessary for GG-NER mediated repair of UV-induced pyrimidine dimers. In vivo, however, where DNA repair occurs in the chromatin context, the UV-DDB complex likely facilitates GG-NER mediated repair irrespective of the DNA damage type.
After DNA damage recognition, the TFIIH complex, together with XPA, verifies the DNA damage and unwinds the DNA helix around the damage, creating an open bubble. Two DNA endonucleases, ERCC5 (XPG) and the complex of ERCC1 and ERCC4 (XPF), excise the oligonucleotide that contains damaged base(s) from the affected DNA strand. DNA polymerases delta, epsilon and/or kappa perform DNA repair synthesis, followed by DNA ligation, thus completing GG-NER.
For a recent review, please refer to Marteijn et al. 2014.
Identifier: R-HSA-6781827
Species: Homo sapiens
Compartment: nucleoplasm
DNA damage in transcribed strands of active genes is repaired through a specialized nucleotide excision repair (NER) pathway known as transcription-coupled nucleotide excision repair (TC-NER). TC-NER impairment is the underlying cause of a severe hereditary disorder Cockayne syndrome, an autosomal recessive disease characterized by hypersensitivity to UV light.
TC-NER is triggered by helix distorting lesions that block the progression of elongating RNA polymerase II (RNA Pol II). Stalled RNA Pol II complex triggers the recruitment of ERCC6. ERCC6, commonly known as CSB (Cockayne syndrome protein B) recruits ERCC8, commonly known as CSA (Cockayne syndrome protein A). ERCC8 has 7 WD repeat motifs and is part of the ubiquitin ligase complex that also includes DDB1, CUL4A or CUL4B and RBX1. The ERCC8 ubiquitin ligase complex is one of the key regulators of TC-NER that probably exerts its role by ubiquitinating one or more factors involved in this repair process, including the RNA Pol II complex and ERCC6.
In addition to RNA Pol II, ERCC6 and the ERCC8 complex, the transcription elongation factor TFIIH, which is also involved in global genome nucleotide excision repair (GG-NER), is recruited to sites of TC-NER. The TC-NER pre-incision complex also includes XPA, XAB2 complex, TCEA1 (TFIIS), HMGN1, UVSSA in complex with USP7, and EP300 (p300). XPA probably contributes to the assembly and stability of the pre-incision complex, similar to its role in GG-NER. The XAB2 complex is involved in pre-mRNA splicing and may modulate the structure of the nascent mRNA hybrid with template DNA through its RNA-DNA helicase activity, allowing proper processing of DNA damage. TCEA1 may be involved in RNA Pol II backtracking, which allows repair proteins to gain access to the damage site. It also facilitates trimming of the 3' end of protruding nascent mRNA from the stalled RNA Pol II, enabling recovery of RNA synthesis after repair.

Deubiquitinating activity of the UVSSA:USP7 complex is needed for ERCC6 stability at repair sites. Non-histone nucleosomal binding protein HMGN1 and histone acetyltransferase p300 (EP300) remodel the chromatin around the damaged site, thus facilitating repair.

Dual incision of the lesion-containing oligonucleotide from the affected DNA strand is performed by two DNA endonucleases, the ERCC1:ERCC4 (ERCC1:XPF) complex and ERCC5 (XPG), which also participate in GG-NER. DNA polymerases delta, epsilon or kappa fill in the single stranded gap after dual incision and the remaining single strand nick is sealed by DNA ligases LIG1 or LIG3 (the latter in complex with XRCC1), similar to GG-NER. After the repair of DNA damage is complete, RNA Pol II resumes RNA synthesis.
For past and recent reviews, see Mellon et al. 1987, Svejstrup 2002, Hanawalt and Spivak 2008, Vermeulen and Fousteri 2013 and Marteijn et al. 2014.

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