Homo sapiens L. (human) [HSA]

FULL NAME: DNA excision repair protein ERCC-1


DESCRIPTION:
Structure-specific DNA repair endonuclease responsible for the 5'-incision during DNA repair.
The function of the ERCC1 protein is predominantly in nucleotide excision repair (NER) of damaged DNA. NER is one of five separate DNA repair mechanisms that also include recombination repair, base excision repair, mismatch repair, and translesion synthesis.
Nucleotide excision repair in eukaryotes is initiated by either Global Genome NER(GG-NER) or Transcription Coupled NER(TC-NER) which involve distinct protein complexes, each recognizing damaged DNA. Thereafter, subsequent steps in GG-NER and TC-NER share a final common excision and repair pathway. Transcription factor II H (TFIIH) separates the abnormal strand from the normal strand. Xeroderma pigmentosum group G (XPG) cuts 3’ to the damaged DNA. Replication protein A (RPA) protects the normal strand. Xeroderma pigmentosum group A (XPA) isolates the damaged segment on the strand to be cut. ERCC1 and xeroderma pigmentosum group F (XPF) cut 5' to the damaged DNA. ERCC1 appears to have a crucial role in stabilizing and enhancing the functionality of the XPF endonuclease. The excised single-stranded DNA of approximately 30 nucleotides and attached NER proteins are removed. DNA polymerases and ligases fill in the gap using the normal strand as a template.

In mammals, the XPF/ERCC1 protein complex also removes nonhomologous 3′ tail ends in homologous recombination. ERCC1 has a role in homology-dependent gene targeting events. In telomere maintenance, XPF/ERCC1 degrades 3′ G-rich overhangs and may have other functions.

ERCC1 knockout mice are runted at birth and die from progressive hepatic insufficiency. Liver failure also occurs in XPF knockout mice, but not mice deficient in any other nucleotide excision repair protein.

Measuring ERCC1 activity may have utility in clinical cancer medicine because one mechanism of resistance to platinum chemotherapy drugs correlates with high ERCC1 activity. Nucleotide excision repair (NER) is the primary DNA repair mechanism that removes the therapeutic platinum-DNA adducts from the tumor DNA. ERCC1 activity levels, being an important part of the NER common final pathway, may serve as a marker of general NER throughput. This has been suggested for patients with gastric, ovarian, colorectal and bladder cancers. In Non-small cell lung carcinoma (NSCLC), surgically removed tumors that receive no further therapy have a better survival if ERCC1-positive than if ERCC1-negative. Thus ERCC1 positivity is a favorable prognostic marker, referring to how the disease will proceed if not further treated. ERCC1-positive NSCLC tumors do not benefit from adjuvant platinum chemotherapy. However, ERCC1-negative NSCLC tumors, prognostically worse without treatment, derive substantial benefit from adjuvant cisplatin-based chemotherapy. High ERCC1 is thus a negative predictive marker, referring to how it will respond to a specific type of treatment.

STRUCTURE SIMILARITY:
Belongs to the ERCC1/RAD10/SWI10 family.


PROTEIN TYPE(S):
DNase
3'-5' exonuclease


RELATED PATHWAY(S):
Fanconi anemia (FA) pathway
nucleotide excision repair (NER)


RELATED DISEASE(S):
cerebro-oculo-facio-skeletal syndrome 4 (COFS4)


RELATED DAMAGE:
intErstrand crosslinks (ICLs)


Amino acids sequence

        10         20         30         40         50         60
MDPGKDKEGV PQPSGPPARK KFVIPLDEDE VPPGVAKPLF RSTQSLPTVD TSAQAAPQTY
        70         80         90        100        110        120
AEYAISQPLE GAGATCPTGS EPLAGETPNQ ALKPGAKSNS IIVSPRQRGN PVLKFVRNVP
       130        140        150        160        170        180
WEFGDVIPDY VLGQSTCALF LSLRYHNLHP DYIHGRLQSL GKNFALRVLL VQVDVKDPQQ
       190        200        210        220        230        240
ALKELAKMCI LADCTLILAW SPEEAGRYLE TYKAYEQKPA DLLMEKLEQD FVSRSLEQLI
       250        260        270
AASREDLALC PGLGPQKARR LFDVLHEPFL KVP  

Encoded by ERCC1 gene

FULL NAME: excision repair cross-complementing rodent repair deficiency, complementation group 1 (includes overlapping antisense sequence)


OTHER NAME(S):
COFS4
RAD10
UV20


DESCRIPTION:
The product of this gene functions in the nucleotide excision repair pathway, and is required for the repair of DNA lesions such as those induced by UV light or formed by electrophilic compounds including cisplatin. The encoded protein forms a heterodimer with the XPF endonuclease (also known as ERCC4), and the heterodimeric endonuclease catalyzes the 5' incision in the process of excising the DNA lesion. The heterodimeric endonuclease is also involved in recombinational DNA repair and in the repair of inter-strand crosslinks. Mutations in this gene result in cerebrooculofacioskeletal syndrome, and polymorphisms that alter expression of this gene may play a role in carcinogenesis. Multiple transcript variants encoding different isoforms have been found for this gene. The last exon of this gene overlaps with the CD3e molecule, epsilon associated protein gene on the opposite strand. [provided by RefSeq, Oct 2009]


Nucleic acid sequence

        10         20         30         40         50         60
atggaccctg ggaaggacaa agagggggtg ccccagccct cagggccgcc agcaaggaag
        70         80         90        100        110        120
aaatttgtga tacccctcga cgaggatgag gtccctcctg gagtggccaa gcccttattc
       130        140        150        160        170        180
cgatctacac agagccttcc cactgtggac acctcggccc aggcggcccc tcagacctac
       190        200        210        220        230        240
gccgaatatg ccatctcaca gcctctggaa ggggctgggg ccacgtgccc cacagggtca
       250        260        270        280        290        300
gagcccctgg caggagagac gcccaaccag gccctgaaac ccggggcaaa atccaacagc
       310        320        330        340        350        360
atcattgtga gccctcggca gaggggcaat cccgtactga agttcgtgcg caatgtgccc
       370        380        390        400        410        420
tgggaatttg gcgacgtaat tcccgactat gtgctgggcc agagcacctg tgccctgttc
       430        440        450        460        470        480
ctcagcctcc gctaccacaa cctgcaccca gactacatcc atgggcggct gcagagcctg
       490        500        510        520        530        540
gggaagaact tcgccttgcg ggtcctgctt gtccaggtgg atgtgaaaga tccccagcag
       550        560        570        580        590        600
gccctcaagg agctggctaa gatgtgtatc ctggccgact gcacattgat cctcgcctgg
       610        620        630        640        650        660
agccccgagg aagctgggcg gtacctggag acctacaagg cctatgagca gaaaccagcg
       670        680        690        700        710        720
gacctcctga tggagaagct agagcaggac ttcgtctccc ggtctctgga acagctcatc
       730        740        750        760        770        780
gccgcatcaa gagaagatct ggccttatgc ccaggcctgg gccctcagaa agcccggagg
       790        800        810        820
ctgtttgatg tcctgcacga gcccttcttg aaagtaccct ga 

Last modification date: Oct. 10, 2011