Aging and cancer: An enzyme protects chromosomes from oxidative damage

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Metaphase chromosomes (blue) of tellurian cancer cells (HeLa) with their telomeres stained in red. Credit: A. Vancevska/J. Lingner (EPFL)

EPFL scientists have identified a protein that caps chromosomes during dungeon multiplication and strengthen them from oxidative repairs and shortening, that are compared with aging and cancer.

When cells divide, they container adult all of their genetic element in a firmly wrapped chromosomes. The ends of a chromosomes have a singular structure, named a telomere. Replication of telomeres requires specialized mechanisms, that adult organisms usually have in a tiny series of cells. This means that chromosomes turn shorter over time, tying a lifespan of cells and contributing to aging. Telomeres are also really supportive to oxidative damage, that affects their ability to replicate. EPFL scientists have now detected a protein that associates with chromosomes during dungeon multiplication and protects their tips from oxidative damage. The discovery, published in Cell Reports, could have poignant implications for how we could yield cancer and other age-related diseases in a future.

Division, damage, and shortening

Precise delivery of a genome from a dungeon to a children is critical to say a characteristics and for a health of a whole organism. Our genome is constantly subjected to repairs from environmental factors such as object and oxygen radicals, that are by-products of a normal metabolic functions. As such, oxidative repairs is a consistent hazard to all life on Earth.

Cells have developed countless antioxidative defenses, though some tools of a cell, like a chromosome tips, a telomeres, are quite unprotected to oxidative damage. Telomeres are sequences of repeated nucleotides during any finish of a chromosome. Their purpose is to strengthen that finish from repairs or from fusing with other chromosomes, that would be inauspicious for a cell. In many adult tissues, each time it divides, a chromosomes digest a small in length; eventually, a telomeres digest so most that a finish of a chromosome becomes exposed, that causes possibly a genocide of a dungeon or an irrevocable retard to serve divisions. This routine is accelerated by oxidative damage. The prevalent speculation of aging, as good as cancer, cites a executive purpose for oxidative repairs of a telomeres in these processes.

An enzyme that protects telomeres

Chromosomes are done adult of DNA that is firmly wound adult around specialized proteins. The labs of Joachim Lingner and Viesturs Simanis during EPFL analyzed a protein make-up of telomeres opposite a whole dungeon cycle to improved know how oxidative repairs affects telomeres during division.

The researchers used a series of molecular biology techniques, including a comparatively new one called QTIP, that labels several proteins in chromosomes so that researchers can review and brand quantitative differences between a protein combination of telomeres in several phases of a life cycle.

The investigate identified an enzyme called Peroxiredoxin 1 (PRDX1). It functions as an antioxidant enzyme, definition that it is used by cells to lessen a effects of oxidative damage.

Using QTIP, a researchers found vast amounts of PRDX1 on telomeres during dual phases of a dungeon cycle: a proviso when a cells synthesizes new DNA and duplicates a genetic element (S-phase), and during a immediately following proviso (G2), when a dungeon grows in distance only before it starts dividing.

Using genetic techniques, a scientist private PRDX1 from a cells, and found that a telomeres were even some-more receptive to oxidative damage. This means that PRDX1 plays an antioxidative purpose that protects telomeres.

In addition, a researchers were means to strew some light onto how oxidative repairs affects telomeres. When they incorporated an oxidatively shop-worn nucleotide into telomeres, they found that a chromosome stopped growing. The reason is that a enzyme called telomerase that builds chromosomes by elongating them abruptly deserted a routine when it encountered a shop-worn nucleotide. As cancer cells need telomerase for presence this anticipating might open adult novel avenues for aggressive this enzyme in cancer.

“Our investigate links oxidative repairs and telomeres, both of that have been formerly related to aging and cancer,” says Joachim Lingner. In serve to these, oxidative repairs of telomeres is also connected to cardiac disaster and robust dystrophy. Having identified PRDX1, Lingner’s lab will now try to establish if there are other antioxidant enzymes that can strengthen telomeres: “We design that serve studies of this problem will yield insights that assistance us know mechanisms of cancer development, aging and hereditary disease.”

Source: EPFL