Nuclear and mitochondrial homologous recombination process to repair DSB by nucleases and helicases

Bernal Muñoz, Manuel

Bernal Muñoz, Manuel · 2019

Abstract

Cells are continuously exposed to different sources of DNA damage agents that can compromise genome stability. Double-strand break (DSB) is one of the most cytotoxic lesions, so faithful repair of DSB is critical to ensure cell viability. Repair of DSBs occurs by direct re-ligation of DNA ends through the non-homologous end-joining (NHEJ) pathway or by the homologous recombination (HR) pathway. Then, cells choose to activate any of these pathways according to their cell cycle progression. The HR pathway repairs the DSBs by using homologous DNA sequence as template for the broken chromosomes. This activity generates joint molecule (JM) intermediates during the different steps of the pathway. JM intermediates are sequentially matured into novel intermediates or dismantled by different specialized proteins (helicases and nucleases) to prevent their progression towards mitosis. Therefore, failure in resolving the JM intermediates results in chromosome segregation defects. Regarding mitochondrial DNA (mtDNA), DNA molecules are constantly damaged as the nuclear DNA and the mtDNA repair process needs to be coordinated with the nucleus activity. For that reason, the majority of the proteins needed for mtDNA repair are imported from the nucleus.

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Nuclear and mitochondrial homologous recombination process to repair DSB by nucleases and helicases

Author: Bernal Muñoz, Manuel

Year: 2019

Source: https://riuma.uma.es/xmlui/bitstream/10630/17209/1/Summary%20Master%20UMA%20Manuel%20Bernal.pdf

DNA damage
nDNA m DNA
m DNA epai
m DNA
deg a acion
m DNA
syn esis
nDNA epai
Un epai ed DSB
N
cell dea h
m DNA
Nuclea and*mi ochond ial*homologous ecombina ion p ocess o*
epai DSB*by*nucleases and*helicases
Cells a e con inuously exposed o di e en sou ces o DNA damage agen s ha can comp omise genome s abili y.
Double-s and b eak (DSB) is one o he mos cy o oxic lesions, so ai h ul epai o DSB is c i ical o ensu e cell iabili y.
Repai o DSBs occu s by di ec e-liga ion o DNA ends h ough he non-homologous end-joining (NHEJ) pa hway o by
he homologous ecombina ion (HR) pa hway.Then, cells choose o ac i a e any o hese pa hways acco ding o hei
cell cycle p og ession.The HR pa hway epai s he DSBs by using homologous DNA sequence as empla e o he b oken
ch omosomes.This ac i i y gene a es join molecule (JM) in e media es du ing he di e en s eps o he pa hway.JM
in e media es a e sequen ially ma u ed in o no el in e media es o disman led by di e en specialized p o eins
(helicases and nucleases) o p e en hei p og ession owa ds mi osis.The e o e, ailu e in esol ing he JM
in e media es esul s in ch omosome seg ega ion de ec s.Rega ding mi ochond ial DNA (m DNA), DNA molecules a e
cons an ly damaged as he nuclea DNA and he m DNA epai p ocess needs o be coo dina ed wi h he nucleus
ac i i y.Fo ha eason, he majo i y o he p o eins needed o m DNA epai a e impo ed om he nucleus.