<\/p>\n
Scientists have finally documented<\/a> a notorious DNA hitchhiker at work in human cells. The team shows how a protein called ORF2p slices DNA at small openings that form during DNA replication.<\/p>\n During this process, a cell makes an identical copy of its genetic material before dividing, then copies its own sequence into the break<\/p>\n This work clarifies why insertions cluster when cells are copying their genomes and how a short sequence motif guides the cut. <\/p>\n It also spells out how the resulting staggered cuts leave telltale short duplications on either side of the new insertion.<\/p>\n LINE-1 and ORF2p<\/p>\n The star here is LINE-1<\/a>, a type of retrotransposon – <\/strong>a mobile genetic element that moves around the genome by copying itself through an RNA intermediate and a DNA-making enzyme. These mobile elements have written roughly one third of our genome over evolutionary time<\/p>\n About 17 percent of our DNA<\/a> consists of LINE-1 sequence, and a small subset remains capable of jumping in modern humans. That activity can reshape genomes and sometimes disrupt genes.<\/p>\n ORF2p has two main jobs: one part cuts DNA, and the other part copies RNA back into DNA. The researchers found that ORF2p sticks to double-stranded DNA by electrical attraction rather than reading specific sequences. <\/p>\n It makes its cut when it finds a small fork-like opening or flap in the DNA a few bases away, following a short pattern of letters near the cutting site.<\/p>\n That structure dependence explains a long standing puzzle. LINE-1 insertions tend to happen while DNA is being copied, because replication creates those forks and flaps that ORF2p recognizes most efficiently. <\/p>\n Stepwise cut leaves a signature<\/p>\n The researchers tracked how ORF2p first nicks the bottom DNA strand at the motif, then reaches the opposite strand a short distance away. <\/p>\n Those two cuts are offset by about 8 to 12 nucleotides, producing the short target site duplications that flank new LINE-1 insertions. <\/p>\n They also found ORF2p holding a mix of RNA and DNA<\/a> in the part of the enzyme that makes new DNA. <\/p>\n This setup lets it start copying its own genetic code right into the cell\u2019s DNA, using the newly opened end of the strand as a starting point for the copy..<\/p>\n Activating ORF2p<\/p>\n When DNA is copied, it briefly forms single strands in certain spots. Those openings are the exact shapes that make ORF2p most active, which helps explain why LINE-1 moves around most during the part of the cell cycle when DNA is being copied.<\/p>\n The flexible tether that links ORF2p\u2019s nuclease to its DNA binding surface gives the enzyme a reach advantage. It can nick one strand, then swing to the other without losing its grip on the binding site. <\/p>\n Other structural snapshots agree that ORF2p can nick the second DNA<\/a> strand during the copying step, reshaping how researchers order the events of insertion. <\/p>\n An interview from the research team described the mechanism as more intricate than scientists had expected. <\/p>\n They noted that the enzyme\u2019s structure revealed a surprisingly complex way of cutting and copying DNA, showing a level of precision that had not been seen before in this kind of genetic activity. <\/p>\n What else the new work adds<\/p>\n The researchers isolated human ORF2p attached to bits of genetic material and captured detailed images of how it connected to both double-stranded DNA and a mix of RNA and DNA. <\/p>\n When they analyzed the attached DNA pieces, they found many came from repetitive regions of the genome, suggesting that ORF2p tends to stick to common, repeat-filled parts of chromosomes.<\/p>\n They also found that ORF2p can reverse transcribe a broad set of cellular RNAs in vitro. That observation helps explain why LINE-1 sometimes ferries other RNAs, including noncoding elements, into the genome.<\/p>\n ORF2p, LINE-1, and human health<\/p>\n LINE-1 activity can break genes, seed rearrangements, and spur mutations that matter in cancer and other conditions. <\/p>\n Those risks scale with how and when ORF2p cuts and copies during cell division, a pattern grounded in decades of work<\/a>. <\/p>\n Better maps of ORF2p contacts and preferences make it easier to predict where insertions might occur in rapidly dividing tissues. <\/p>\n That could guide surveillance in tumors or help interpret puzzling mutations that turn up in clinical genomes.<\/p>\n The new structure focused on ORF2p in action, but earlier work had already solved the ORF2p core and mapped how its reverse transcriptase grips template RNA, offering a framework for inhibitor design.<\/p>\n Together, these findings point to possible ways to slow LINE-1 movement, such as stopping the enzyme from cutting forked DNA<\/a> or preventing it from starting to copy at the beginning of an RNA strand rich in adenine bases.<\/p>\n Therapeutic ideas are still early. The clearer the mechanism becomes, the more specific and safer those strategies can be.<\/p>\n The study is published in Science<\/a>.<\/p>\n —–<\/p>\n Like what you read? Subscribe to our newsletter<\/a> for engaging articles, exclusive content, and the latest updates. <\/p>\n Check us out on EarthSnap<\/a>, a free app brought to you by Eric Ralls<\/a> and Earth.com.<\/p>\n —–<\/p>\n","protected":false},"excerpt":{"rendered":"Scientists have finally documented a notorious DNA hitchhiker at work in human cells. The team shows how a…\n","protected":false},"author":2,"featured_media":132799,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[272],"tags":[9,79506,18,458,19,17,3136,11929,133,79505],"class_list":{"0":"post-132798","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-genetics","8":"tag-breaking-news","9":"tag-earth-com","10":"tag-eire","11":"tag-genetics","12":"tag-ie","13":"tag-ireland","14":"tag-local-news","15":"tag-newsbreak","16":"tag-science","17":"tag-scientists-watch-humans-most-active-parasite-gene-cutting-dna"},"share_on_mastodon":{"url":"","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/posts\/132798","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/comments?post=132798"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/posts\/132798\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/media\/132799"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/media?parent=132798"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/categories?post=132798"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/tags?post=132798"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}