Genetically engineered mice with disabling mutations in ERCC1 have defects in DNA repair, accompanied by metabolic stress-induced changes in physiology that result in premature aging.

[9] Reflecting this cross-species genetic complementation method, the gene was called “Excision repair cross-complementing 1”.

Several models have been proposed for binding of ERCC1–XPF to DNA, based on partial structures of relevant protein fragments at atomic resolution.

[19][20] The relevant activity of ERCC1–XPF for both types of double-strand break repair is the ability to remove non-homologous 3′ single-stranded tails from DNA ends before rejoining.

Trimming of 3’ single-stranded tail is also needed in a mechanistically distinct subpathway of non-homologous end-joining, dependent on the Ku proteins.

[17] Homologous integration of DNA, an important technique for genetic manipulation, is dependent on the function of ERCC1-XPF in the host cell.

Alternatively, a double-strand break may be made in the DNA near the ICL, and subsequent homologous recombination repair may involve ERCC1-XPF action.

[8][27] COFS syndrome is a rare recessive disorder in which affected individuals undergo rapid neurologic decline and indications of accelerated aging.

[31] 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.

However, ERCC1-negative NSCLC tumors, prognostically worse without treatment, derive substantial benefit from adjuvant cisplatin-based chemotherapy.

Thus, European Society for Medical Oncology (ESMO) has not recommended ERCC1 testing prior to the use of oxaliplatin in routine practice.

During Cd-induced malignant transformation, the promoter regions of ERCC1, as well as of hMSH2, XRCC1, and hOGG1, were heavily methylated and both the messenger RNA and proteins of these DNA repair genes were progressively reduced.

A translational level control of ERCC1, due to a microRNA (miRNA), has been shown during HIV viral infection.

A trans-activation response element (TAR) miRNA, coded for by the HIV virus, down-regulates ERCC1 protein expression.

[43] TAR miRNA allows ERCC1 mRNA to be transcribed, but acts at the p-body level to prevent translation of ERCC1 protein.

(A p-body is a cytoplasmic granule “processing body” that interacts with miRNAs to repress translation or trigger degradation of target RNAs.)

In breast cancer cell lines, almost one third (55/167) of miRNA promoters were targets for aberrant methylation (epigenetic repression).

HMGA proteins are characterized by three DNA-binding domains, called AT-hooks, and an acidic carboxy-terminal tail.

They do not display direct transcriptional activation capacity, but regulate gene expression by changing local DNA conformation.

Regulation is achieved by binding to AT-rich regions in the DNA and/or direct interaction with several transcription factors.

[citation needed] DNA repair-deficient Ercc1 mutant mice show numerous features of accelerated aging, and have a limited lifespan.

[48] It appears that in Ercc1 mutant mice dietary restriction while delaying aging also attenuates accumulation of genome-wide DNA damage and preserves transcriptional output, likely contributing to improved cell viability.

[50] The DNA repair function of Ercc1 appears to be required in both male and female germ cells at all stages of their maturation.

Age-related macular degeneration (AMD) of the retina is the leading cause of blindness in people over age fifty.

[51] The retina is the highest oxygen consuming tissue in the human body and thus prone to oxidative damages.