Cut-and-Run: A Distinct Mechanism by which V(D)J Recombination Causes Genome Instability

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60076658%3A12310%2F19%3A43899315" target="_blank" >RIV/60076658:12310/19:43899315 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.cell.com/molecular-cell/pdf/S1097-2765(19)30136-4.pdf" target="_blank" >https://www.cell.com/molecular-cell/pdf/S1097-2765(19)30136-4.pdf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.molcel.2019.02.025" target="_blank" >10.1016/j.molcel.2019.02.025</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Cut-and-Run: A Distinct Mechanism by which V(D)J Recombination Causes Genome Instability

Popis výsledku v původním jazyce

V(D)J recombination is essential to generate antigen receptor diversity but is also a potent cause of genome instability. Many chromosome alterations that result from aberrant V(D)J recombination involve breaks at single recombination signal sequences (RSSs). A long-standing question, however, is how such breaks occur. Here, we show that the genomic DNA that is excised during recombination, the excised signal circle (ESC), forms a complex with the recombinase proteins to efficiently catalyze breaks at single RSSs both in vitro and in vivo. Following cutting, the RSS is released while the ESC-recombinase complex remains intact to potentially trigger breaks at further RSSs. Consistent with this, chromosome breaks at RSSs increase markedly in the presence of the ESC. Notably, these breaks co-localize with those found in acute lymphoblastic leukemia patients and occur at key cancer driver genes. We have named this reaction &quot;cut-and-run&quot; and suggest that it could be a significant cause of lymphocyte genome instability.

Název v anglickém jazyce

Cut-and-Run: A Distinct Mechanism by which V(D)J Recombination Causes Genome Instability

Popis výsledku anglicky

V(D)J recombination is essential to generate antigen receptor diversity but is also a potent cause of genome instability. Many chromosome alterations that result from aberrant V(D)J recombination involve breaks at single recombination signal sequences (RSSs). A long-standing question, however, is how such breaks occur. Here, we show that the genomic DNA that is excised during recombination, the excised signal circle (ESC), forms a complex with the recombinase proteins to efficiently catalyze breaks at single RSSs both in vitro and in vivo. Following cutting, the RSS is released while the ESC-recombinase complex remains intact to potentially trigger breaks at further RSSs. Consistent with this, chromosome breaks at RSSs increase markedly in the presence of the ESC. Notably, these breaks co-localize with those found in acute lymphoblastic leukemia patients and occur at key cancer driver genes. We have named this reaction &quot;cut-and-run&quot; and suggest that it could be a significant cause of lymphocyte genome instability.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Molecular Cell

ISSN

1097-2765

e-ISSN

—

Svazek periodika

74

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

23

Strana od-do

584-597,"e9"

Kód UT WoS článku

000466703900017

EID výsledku v databázi Scopus

2-s2.0-85064875948