Результаты исследований: Научные публикации в периодических изданиях › обзорная статья › Рецензирование
Aberrant base excision repair pathway of oxidatively damaged DNA : Implications for degenerative diseases. / Talhaoui, Ibtissam; Matkarimov, Bakhyt T.; Tchenio, Thierry и др.
в: Free Radical Biology and Medicine, Том 107, 01.06.2017, стр. 266-277.Результаты исследований: Научные публикации в периодических изданиях › обзорная статья › Рецензирование
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TY - JOUR
T1 - Aberrant base excision repair pathway of oxidatively damaged DNA
T2 - Implications for degenerative diseases
AU - Talhaoui, Ibtissam
AU - Matkarimov, Bakhyt T.
AU - Tchenio, Thierry
AU - Zharkov, Dmitry O.
AU - Saparbaev, Murat K.
N1 - Publisher Copyright: © 2017 Elsevier Inc.
PY - 2017/6/1
Y1 - 2017/6/1
N2 - In cellular organisms composition of DNA is constrained to only four nucleobases A, G, T and C, except for minor DNA base modifications such as methylation which serves for defence against foreign DNA or gene expression regulation. Interestingly, this severe evolutionary constraint among other things demands DNA repair systems to discriminate between regular and modified bases. DNA glycosylases specifically recognize and excise damaged bases among vast majority of regular bases in the base excision repair (BER) pathway. However, the mismatched base pairs in DNA can occur from a spontaneous conversion of 5-methylcytosine to thymine and DNA polymerase errors during replication. To counteract these mutagenic threats to genome stability, cells evolved special DNA repair systems that target the non-damaged DNA strand in a duplex to remove mismatched regular DNA bases. Mismatch-specific adenine- and thymine-DNA glycosylases (MutY/MUTYH and TDG/MBD4, respectively) initiated BER and mismatch repair (MMR) pathways can recognize and remove normal DNA bases in mismatched DNA duplexes. Importantly, in DNA repair deficient cells bacterial MutY, human TDG and mammalian MMR can act in the aberrant manner: MutY and TDG removes adenine and thymine opposite misincorporated 8-oxoguanine and damaged adenine, respectively, whereas MMR removes thymine opposite to O6-methylguanine. These unusual activities lead either to mutations or futile DNA repair, thus indicating that the DNA repair pathways which target non-damaged DNA strand can act in aberrant manner and introduce genome instability in the presence of unrepaired DNA lesions. Evidences accumulated showing that in addition to the accumulation of oxidatively damaged DNA in cells, the aberrant DNA repair can also contribute to cancer, brain disorders and premature senescence. For example, the aberrant BER and MMR pathways for oxidized guanine residues can lead to trinucleotide expansion that underlies Huntington's disease, a severe hereditary neurodegenerative syndrome. This review summarises the present knowledge about the aberrant DNA repair pathways for oxidized base modifications and their possible role in age-related diseases.
AB - In cellular organisms composition of DNA is constrained to only four nucleobases A, G, T and C, except for minor DNA base modifications such as methylation which serves for defence against foreign DNA or gene expression regulation. Interestingly, this severe evolutionary constraint among other things demands DNA repair systems to discriminate between regular and modified bases. DNA glycosylases specifically recognize and excise damaged bases among vast majority of regular bases in the base excision repair (BER) pathway. However, the mismatched base pairs in DNA can occur from a spontaneous conversion of 5-methylcytosine to thymine and DNA polymerase errors during replication. To counteract these mutagenic threats to genome stability, cells evolved special DNA repair systems that target the non-damaged DNA strand in a duplex to remove mismatched regular DNA bases. Mismatch-specific adenine- and thymine-DNA glycosylases (MutY/MUTYH and TDG/MBD4, respectively) initiated BER and mismatch repair (MMR) pathways can recognize and remove normal DNA bases in mismatched DNA duplexes. Importantly, in DNA repair deficient cells bacterial MutY, human TDG and mammalian MMR can act in the aberrant manner: MutY and TDG removes adenine and thymine opposite misincorporated 8-oxoguanine and damaged adenine, respectively, whereas MMR removes thymine opposite to O6-methylguanine. These unusual activities lead either to mutations or futile DNA repair, thus indicating that the DNA repair pathways which target non-damaged DNA strand can act in aberrant manner and introduce genome instability in the presence of unrepaired DNA lesions. Evidences accumulated showing that in addition to the accumulation of oxidatively damaged DNA in cells, the aberrant DNA repair can also contribute to cancer, brain disorders and premature senescence. For example, the aberrant BER and MMR pathways for oxidized guanine residues can lead to trinucleotide expansion that underlies Huntington's disease, a severe hereditary neurodegenerative syndrome. This review summarises the present knowledge about the aberrant DNA repair pathways for oxidized base modifications and their possible role in age-related diseases.
KW - 8-oxo-7,8-dihydroguanine, purine 8,5′-cyclo-2′-deoxyribonucleosides, base excision repair
KW - AP endonuclease
KW - DNA glycosylase, nucleotide incision repair
KW - Mismatch repair
KW - Nucleotide excision repair, trinucleotide expansion
KW - Oxidatively damaged DNA
KW - Oxidation-Reduction
KW - Oxidative Stress
KW - Humans
KW - DNA Repair/genetics
KW - Neurodegenerative Diseases/genetics
KW - Neoplasms/genetics
KW - Animals
KW - DNA/chemistry
KW - Cellular Senescence
KW - DNA Damage
UR - http://www.scopus.com/inward/record.url?scp=85007504937&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2016.11.040
DO - 10.1016/j.freeradbiomed.2016.11.040
M3 - Review article
C2 - 27890638
AN - SCOPUS:85007504937
VL - 107
SP - 266
EP - 277
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
SN - 0891-5849
ER -
ID: 8672535