{"id":6463,"date":"2026-10-19T09:48:56","date_gmt":"2026-10-19T09:48:56","guid":{"rendered":"https:\/\/phd.hi.is\/doktorsvorn\/doktorsvorn-i-lif-og-laeknavisindum-thejus-b-venkatesh\/"},"modified":"2026-10-19T09:48:56","modified_gmt":"2026-10-19T09:48:56","slug":"doktorsvorn-i-lif-og-laeknavisindum-thejus-b-venkatesh","status":"publish","type":"phd_defence","link":"https:\/\/phd.hi.is\/en\/doktorsvorn\/doktorsvorn-i-lif-og-laeknavisindum-thejus-b-venkatesh\/","title":{"rendered":"Doktorsv\u00f6rn \u00ed l\u00edf- og l\u00e6knav\u00edsindum Thejus B. Venkatesh"},"content":{"rendered":"
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Mi\u00f0vikudaginn 4. mars ver Thejus B. Venkatesh doktorsritger\u00f0 s\u00edna \u00ed l\u00edf- og l\u00e6knav\u00edsindum vi\u00f0 L\u00e6knadeild H\u00e1sk\u00f3la \u00cdslands.<\/p>\n

Ritger\u00f0in ber heiti\u00f0: Hlutverk MITF-A \u00eds\u00f3formsins \u00ed vi\u00f0haldi \u00e1 st\u00f6\u00f0ugleika erf\u00f0amengisins. A Novel Role of the MITF-A Isoform in Maintaining Genomic Stability.<\/p>\n

Andm\u00e6lendur eru dr. Lum\u00edr Krej\u010d\u00ed, yfirma\u00f0ur ranns\u00f3knarh\u00f3ps vi\u00f0 Masaryk University \u00ed Brno, T\u00e9kklandi, og dr. Libor Mac\u016frek, yfirma\u00f0ur ranns\u00f3knastofu vi\u00f0 Institute of Molecular Genetics of the Czech Academy of Sciences \u00ed Prag, T\u00e9kklandi.<\/p>\n

Umsj\u00f3narkennari var Stef\u00e1n \u00de. Sigur\u00f0sson, pr\u00f3fessor og lei\u00f0beinandi var Linda Vi\u00f0arsd\u00f3ttir, lektor. Auk \u00feeirra s\u00e1tu \u00ed doktorsnefnd Eir\u00edkur Steingr\u00edmsson, pr\u00f3fessor og \u00deorkell Gu\u00f0j\u00f3nsson, d\u00f3sent.<\/p>\n

Sveinn H\u00e1kon Har\u00f0arson, d\u00f3sent og forst\u00f6\u00f0uma\u00f0ur l\u00edfv\u00edsinda, stj\u00f3rnar ath\u00f6fninni sem fer fram \u00ed H\u00e1t\u00ed\u00f0arsal H\u00e1sk\u00f3la \u00cdslands og hefst kl. 13.00.<\/p>\n

\u00c1grip<\/strong><\/p>\n

Erf\u00f0amengi allra lifandi frumna er vi\u00f0kv\u00e6mt fyrir margv\u00edslegu \u00e1reiti sem getur haft \u00e1hrif \u00e1 st\u00f6\u00f0ugleika \u00feess. Nau\u00f0synlegt er a\u00f0 vi\u00f0halda st\u00f6\u00f0ugleika erf\u00f0amengisins fyrir e\u00f0lilega frumustarfsemi, \u00fear sem r\u00f6skun \u00e1 \u00feessum ferlum getur leitt til myndunar krabbameina og annarra sj\u00fakd\u00f3ma. \u00deegar DNA skemmdir ver\u00f0a virkja frumur svokalla\u00f0 DNA skemmdarvi\u00f0brag\u00f0 sem samh\u00e6fir frumuhrings stj\u00f3rnun og vi\u00f0ger\u00f0arferli sem vi\u00f0halda st\u00f6\u00f0ugleika erf\u00f0aefnisins. \u00c1lag vi\u00f0 DNA eftirmyndun getur einnig valdi\u00f0 erf\u00f0afr\u00e6\u00f0ilegum \u00f3st\u00f6\u00f0ugleika, me\u00f0al annars \u00feegar eftirmyndunargaffall st\u00f6\u00f0vast og r\u00f6skun ver\u00f0ur \u00e1 eftirmyndunarferlinu. Langvarandi \u00e1lag vi\u00f0 DNA eftirmyndun getur leitt til litningagalla og DNA-skemmda sem lei\u00f0ir til upps\u00f6fnunar \u00e1 st\u00f6kkbreytingum sem er eitt helsta einkenni krabbameina.<\/p>\n

MITF er umritunar\u00fe\u00e1ttur sem er \u00feekktastur fyrir hlutverk sitt \u00ed l\u00edffr\u00e6\u00f0i sortufrumna og sortu\u00e6xla en hlutverk hans \u00ed vi\u00f0haldi st\u00f6\u00f0ugleika erf\u00f0amengisins hefur l\u00edti\u00f0 veri\u00f0 rannsaka\u00f0. Ranns\u00f3knir hafa einkum beinst a\u00f0 MITF-M \u00eds\u00f3forminu, sem tj\u00e1\u00f0 er \u00ed sortufrumum og sortu\u00e6xlum. Hlutverk annarra MITF-\u00eds\u00f3forma er mun s\u00ed\u00f0ur skilgreint, en frumur a\u00f0rar en sortufrumur tj\u00e1 a\u00f0allega MITF-A \u00eds\u00f3formi\u00f0.<\/p>\n

Markmi\u00f0 \u00feessa verkefnis var a\u00f0 rannsaka hlutverk MITF-A \u00eds\u00f3formsins betur. Ranns\u00f3knin s\u00fdndi a\u00f0 MITF-A \u00eds\u00f3formi\u00f0 er tj\u00e1\u00f0 \u00ed flestum vefjum, \u00fear \u00e1 me\u00f0al \u00ed \u00e6xlisvef, og gegnir hlutverki \u00ed vi\u00f0haldi \u00e1 st\u00f6\u00f0ugleika erf\u00f0amengisins. Beinkrabbameinsfrumul\u00ednan U2OS var notu\u00f0 til a\u00f0 rannsaka hlutverk MITF-A. Ni\u00f0urst\u00f6\u00f0ur s\u00fdndu a\u00f0 hindrun \u00e1 tj\u00e1ningu MITF-A lei\u00f0ir til TP53 upps\u00f6fnunar, aukinnar tj\u00e1ningar \u00e1 P21 og fj\u00f6lgun 53BP1-bletta \u00ed kjarna. Massagreining leiddi \u00ed lj\u00f3s a\u00f0 MITF-A binst \u00ed r\u00edkara m\u00e6li pr\u00f3teinum sem taka \u00fe\u00e1tt \u00ed DNA eftirmyndun og DNA vi\u00f0ger\u00f0, \u00fear \u00e1 me\u00f0al RPA og PARP1, samanbori\u00f0 vi\u00f0 MITF-M. Frekari ranns\u00f3knir s\u00fdndu a\u00f0 vi\u00f0 MITF-A skort eykst hra\u00f0i DNA eftirmyndunar, sem bendir til verndandi hlutverks MITF-A \u00ed S-fasa frumuhringsins og \u00fe\u00e1ttt\u00f6ku \u00feess \u00ed vi\u00f0haldi \u00e1 st\u00f6\u00f0ugleika erf\u00f0aefnisins. Samhli\u00f0a \u00feessu minnka\u00f0i tj\u00e1ning gena sem tengjast DNA eftirmyndun og DNA vi\u00f0ger\u00f0.<\/p>\n

Ni\u00f0urst\u00f6\u00f0ur \u00feessarar ranns\u00f3knar varpa \u00feannig lj\u00f3si \u00e1 \u00e1\u00f0ur l\u00edtt \u00feekkt hlutverk MITF-A \u00ed DNA-eftirmyndun og \u00ed vi\u00f0haldi \u00e1 st\u00f6\u00f0ugleika erf\u00f0amengisins.<\/p>\n

Abstract<\/strong><\/p>\n

The genome of all living cells is susceptible to various intra- and extracellular events that can compromise its stability. This genomic stability is crucial for the normal function of all cells, and failure to preserve genome integrity can lead to cancer and other diseases. In the event of DNA damage, cells activate the so-called DNA Damage Response to initiate DNA repair. Replication stress can also cause genomic instability. Replication stress interrupts the DNA replication process by stalling the active replication fork. If there is prolonged replication stress, it leads to genomic instability, which can result in DNA damage, chromosomal abnormalities, and mutations. MITF is a transcription factor best known for its roles in melanocyte biology and melanoma, but its function in genome maintenance remains incompletely understood. While most studies have focused on the MITF-M isoform, the roles of other isoforms remain largely unexplored. Interestingly, many non-melanocytic cells predominantly express the MITF-A isoform. Data presented in this project show that MITF-A is expressed in most tissues, including cancer tissues, and may function as a genome maintenance protein. In this study, we use the osteosarcoma cell line U2OS to uncover the non-melanocyte-specific role of MITF. We found that MITF depletion leads to TP53 accumulation, P21 expression, increased 53BP1 nuclear bodies, and high fork speed, suggesting a protective role in S phase, thus maintaining genomic stability. Differentially expressed genes upon MITF-A isoform knockdown show downregulation of genes associated with DNA replication and DNA repair. Mass spectrometry reveals that MITF-A shows increased interaction with proteins involved in DNA replication and repair, including RPA and PARP1, compared to MITF-M. Notably, data from single-molecule C-trap optical tweezer experiments show that MITF-A, but not MITF-M, stably binds RPA-coated single-stranded DNA. Replication dynamics revealed that MITF-A depletion led to an increase in replication fork speed, which is associated with reduced PARylation. Collectively, this study highlights MITF-A\u2019s role in DNA replication and in maintaining genomic stability.<\/p>\n

Um doktorsefni\u00f0<\/strong><\/p>\n

Thejus Byranayakanahalli Venkatesh f\u00e6ddist \u00e1ri\u00f0 1995 \u00ed Bengaluru \u00e1 Indlandi. Hann lauk h\u00e1sk\u00f3lan\u00e1mi \u00ed fiskifr\u00e6\u00f0i vi\u00f0 Karnataka Veterinary, Animal and Fisheries Sciences University \u00e1ri\u00f0 2017.<\/p>\n

Thejus lauk meistaragr\u00e1\u00f0u \u00ed stofnfrumut\u00e6kni \u00e1ri\u00f0 2019 fr\u00e1 Manipal Institute of Regenerative Medicine vi\u00f0 Manipal University \u00e1 Indlandi. Hann vann meistararitger\u00f0 s\u00edna \u00e1 ranns\u00f3knastofu pr\u00f3fessors Colins Jamora \u00fear sem hann rannsaka\u00f0i s\u00fdklalyfjavirk pept\u00ed\u00f0 \u00ed s\u00e1ragr\u00e6\u00f0slu og bandvefsmyndun (fibrosis) vi\u00f0 Centre for Inflammation and Tissue Homeostasis, Institute for Stem Cell Biology \u00ed Bengaluru.<\/p>\n

Foreldrar hans eru Venkatesh Murthy og Lakshmi Venkatesh.<\/p>\n<\/div><\/div>","protected":false},"featured_media":5881,"template":"","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"default","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","ast-disable-related-posts":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"_phd_date_start":"2026-03-04T13:00:00+00:00","_phd_date_end":"2026-03-04T16:00:00+00:00","_phd_location":"A\u00f0albygging H\u00e1t\u00ed\u00f0asalur","_phd_admission":"A\u00f0gangur \u00f3keypis","_phd_thesis_title":"Hlutverk MITF-A \u00eds\u00f3formsins \u00ed vi\u00f0haldi \u00e1 st\u00f6\u00f0ugleika erf\u00f0amengisins. A Novel Role of the MITF-A Isoform in Maintaining Genomic Stability","_phd_source_url":"https:\/\/gamli.hi.is\/vidburdir\/doktorsvorn_i_lif_og_laeknavisindum_thejus_b_venkatesh","_phd_source_node_id":"443428","_phd_source_type":"vidburdir","_phd_member_id":1006,"footnotes":""},"phd_school":[60,67],"phd_discipline":[70],"class_list":["post-6463","phd_defence","type-phd_defence","status-publish","has-post-thumbnail","hentry","phd_school-heilbrigdisvisindasvid","phd_school-laeknadeild","phd_discipline-phd-i-lif-og-laeknavisindum"],"_links":{"self":[{"href":"https:\/\/phd.hi.is\/en\/wp-json\/wp\/v2\/phd_defence\/6463","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/phd.hi.is\/en\/wp-json\/wp\/v2\/phd_defence"}],"about":[{"href":"https:\/\/phd.hi.is\/en\/wp-json\/wp\/v2\/types\/phd_defence"}],"version-history":[{"count":0,"href":"https:\/\/phd.hi.is\/en\/wp-json\/wp\/v2\/phd_defence\/6463\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/phd.hi.is\/en\/wp-json\/wp\/v2\/media\/5881"}],"wp:attachment":[{"href":"https:\/\/phd.hi.is\/en\/wp-json\/wp\/v2\/media?parent=6463"}],"wp:term":[{"taxonomy":"phd_school","embeddable":true,"href":"https:\/\/phd.hi.is\/en\/wp-json\/wp\/v2\/phd_school?post=6463"},{"taxonomy":"phd_discipline","embeddable":true,"href":"https:\/\/phd.hi.is\/en\/wp-json\/wp\/v2\/phd_discipline?post=6463"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}