{"id":4658,"date":"2015-01-29T15:12:40","date_gmt":"2015-01-29T20:12:40","guid":{"rendered":"http:\/\/geiselmed.dartmouth.edu\/news\/?p=4658"},"modified":"2015-02-13T15:24:10","modified_gmt":"2015-02-13T20:24:10","slug":"dartmouth-researchers-determine-key-element-in-circadian-clock-speed","status":"publish","type":"post","link":"https:\/\/geiselmed.dartmouth.edu\/news\/2015\/dartmouth-researchers-determine-key-element-in-circadian-clock-speed\/","title":{"rendered":"Dartmouth Researchers Determine Key Element in Circadian Clock Speed"},"content":{"rendered":"

In a discovery that may lead to new treatments for sleep disorders, jet lag and other health problems tied to circadian rhythms, researchers at Dartmouth\u2019s Geisel School of Medicine have identified a determinant of the circadian clock\u2019s period. Their findings appear in the January 29th issue of Science<\/em> magazine<\/a>.<\/p>\n

Whether in fungi or human beings, circadian clocks influence nearly all aspects of an organism\u2019s life. On a molecular level at the core of these circadian rhythms, biological oscillators are present and key proteins comprising these cycles have a lifetime of approximately 24 hours.\u00a0 Because the period of the clock matched the lifetime of the proteins it was assumed for many years that the stability of the protein determined the period length of these biological clocks.\u00a0 But it\u2019s not that simple.<\/p>\n

Why this turnover occurs within 24 hours has long been attributed to the clock proteins themselves, which undergo coordinated and progressive modification\u2014actually phosphorylation, which modifies protein structure and activity\u2014leading to degradation and turnover. Essentially, clock proteins are slowly phosphorylated until they become unstable and disappear allowing the cycle of synthesis and destruction to start again.<\/p>\n

\"Distinct<\/a>
Distinct roles for FRQ phosphorylation and degradation in the clock.<\/strong>
White Collar-1 and -2 (WC-1 and WC-2) activate frq expression and FRQ (with FRH and CK1) later inhibit expression. FRQ phosphorylation affects interactions with WC-1\/WC-2, reducing inhibition. By influencing these key interactions, FRQ phosphorylations determine the rate at which core clock events, those within the clock face, occur. After key phosphorylations close the loop, degradation-related events need not affect circadian period.<\/figcaption><\/figure>\n

By examining in a well known model organism the factors leading to period determination\u2014and the longstanding causal loop uniting clock protein phosphorylation with stability\u2014Dartmouth researchers have pinned down the determinant of the clock\u2019s period.<\/p>\n

\u201cWe all used to think the circadian cycle ended when the important clock protein was degraded,\u201d says Principal Investigator Jay Dunlap, PhD, professor of genetics and biochemistry and chair of the Department of Genetics, \u201cand that period length was determined in large part by how stable those proteins were.\u201d<\/p>\n

But Dunlap\u2019s team, in work supported by the U.S. National Institute of General Medical Sciences and done in collaboration with the lab of Luis Larrondo from the Pontificia Universidad Cat\u00f3lica de Chile, found that phosphorylation itself was sufficient to change the effectiveness of the protein in the negative feedback of the oscillator so that the clock protein was no longer effective in feedback. Although protein degradation is the final outcome, protein structure, not changes in stability, may actually be the key element determining clock speed.<\/p>\n

\u201cSurprisingly, we found that stability is not the key factor in period determination,\u201d Dunlap says. \u201cOnce phosphorylation has passed a certain point it doesn\u2019t matter whether or not the clock protein has degraded because at that point it is invisible to the clock machinery.<\/p>\n

\u201cThe circadian clock influences our daily lives in more ways than we can count,\u201d Dunlap says, \u201cand this work points to how the clock might be manipulated to improve health.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":"

In a discovery that may lead to new treatments for sleep disorders, jet lag and other health problems tied to circadian rhythms, researchers have identified a determinant of the circadian clock\u2019s period. Their findings appear in the January 29th issue of Science<\/i> magazine. <\/p>\n","protected":false},"author":12,"featured_media":4659,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"aside","meta":{"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[1,8],"tags":[114,507,506,41,505,320,504],"class_list":["post-4658","post","type-post","status-publish","format-aside","has-post-thumbnail","hentry","category-news","category-research","tag-biochemistry","tag-circadian-clock","tag-circadian-rhythm","tag-genetics","tag-jay-dunlap","tag-research-2","tag-sleep-disorders","post_format-post-format-aside","author-12"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"https:\/\/geiselmed.dartmouth.edu\/news\/wp-content\/uploads\/sites\/2\/2015\/01\/alarm-clock-stock.jpg","jetpack_sharing_enabled":true,"jetpack_shortlink":"https:\/\/wp.me\/p4r3h1-1d8","_links":{"self":[{"href":"https:\/\/geiselmed.dartmouth.edu\/news\/wp-json\/wp\/v2\/posts\/4658","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/geiselmed.dartmouth.edu\/news\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/geiselmed.dartmouth.edu\/news\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/geiselmed.dartmouth.edu\/news\/wp-json\/wp\/v2\/users\/12"}],"replies":[{"embeddable":true,"href":"https:\/\/geiselmed.dartmouth.edu\/news\/wp-json\/wp\/v2\/comments?post=4658"}],"version-history":[{"count":4,"href":"https:\/\/geiselmed.dartmouth.edu\/news\/wp-json\/wp\/v2\/posts\/4658\/revisions"}],"predecessor-version":[{"id":4662,"href":"https:\/\/geiselmed.dartmouth.edu\/news\/wp-json\/wp\/v2\/posts\/4658\/revisions\/4662"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/geiselmed.dartmouth.edu\/news\/wp-json\/wp\/v2\/media\/4659"}],"wp:attachment":[{"href":"https:\/\/geiselmed.dartmouth.edu\/news\/wp-json\/wp\/v2\/media?parent=4658"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/geiselmed.dartmouth.edu\/news\/wp-json\/wp\/v2\/categories?post=4658"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/geiselmed.dartmouth.edu\/news\/wp-json\/wp\/v2\/tags?post=4658"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}