MUTYH

Last updated
MUTYH
Protein MUTYH PDB 1x51.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases MUTYH , MYH, mutY DNA glycosylase, mutY homolog (E. coli)
External IDs OMIM: 604933 MGI: 1917853 HomoloGene: 8156 GeneCards: MUTYH
Orthologs
SpeciesHumanMouse
Entrez

4595

70603

Ensembl

ENSG00000132781

ENSMUSG00000028687

UniProt

Q9UIF7

Q99P21

RefSeq (mRNA)

NM_001159581
NM_133250
NM_001316747

RefSeq (protein)

NP_001153053
NP_001303676
NP_573513

Location (UCSC) Chr 1: 45.33 – 45.34 Mb Chr 4: 116.66 – 116.68 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

MUTYH (mutY DNA glycosylase) is a human gene that encodes a DNA glycosylase, MUTYH glycosylase. It is involved in oxidative DNA damage repair and is part of the base excision repair pathway. The enzyme excises adenine bases from the DNA backbone at sites where adenine is inappropriately paired with guanine, cytosine, or 8-oxo-7,8-dihydroguanine, a common form of oxidative DNA damage.

The protein is localized to the nucleus and mitochondria. Mutations in this gene result in heritable predisposition to colon and stomach cancer. Multiple transcript variants encoding different isoforms have been found for this gene. [5]

Location and structure

MUTYH has its locus on the short (p) arm of chromosome 1 (1p34.1), from base pair 45,464,007 to base pair 45,475,152 (45,794,835–45,806,142). The gene is composed of 16 exons and has a size of 546 amino acids [6] and is approximately 7.1kb. [7] The presence of disulfide crosslinking gives rise to a complex crystal structure of the MUTY-DNA. [8] The protein structure of the MUTYH gene has its N-terminal on the 5’ and the C-terminal on the 3’. Within the N-terminal, there is a helix-hairpin-helix and pseudo helix-hairpin-helix in addition to an iron cluster motif.

Mechanism

Repair of oxidative DNA damage is the result of a collaborative effort of MUTYH, OGG1, and MTH1. MUTYH acts on the adenine base that is mispaired to 8-oxoG, while OGG1 detects and acts on 8-oxoG, removing it. [9] [10] TP53 transcriptionally regulates MUTYH and may potentially act as a regulator for p53. [11]

Expression

MUTYH is overexpressed in CD4-T cells, the prostate, the colon, where cells frequently divide, and the rectum. There is evidence of MUTYH expression in kidney, intestinal, nervous system and muscle tissues. [6]

Protein interactions

MUTYH has been shown to interact with Replication protein A1, [12] PCNA [12] and APEX1. [12]

MUTYH and OGG1 excision of bases causes the formation of apurinic/ apyrimidinic sites (AP sites). These sites are mutagenic in nature and require constant and immediate repair which is achieved by the active involvement of protein complexes that repair the AP site via short and long patch repair pathways. The short patch repair pathway employs POLB (DNA polymerase beta), APE1, XRCC1, PARP1 with the addition of either the LIG1 or LIG3 genes. When an insertion of one nucleotide occurs, the enzyme AP endonuclease (APEX/APE1) cuts out the mismatched base pairs at the AP site and this causes the evolvement of 5’dRP (5’ deoxyribose phosphate), a terminal blocking group, and 3’-OH ( 3’ hydroxyl end). POLB is required to remove the 5’dRP, and it does this by enzymatic activity, namely polymerase and dRP lyase. DNA ligase is used to seal the fragments after dRP excision causes the formation of 5’PO4 that is necessary to form the phosphodiester bonds of DNA. The purpose of PARP1 and XRCC1 in the single strand break repair pathway, is to stabilize the strands of DNA while they undergo repair, synthesis, gap-filling and ligation. PARP1 acts as a recruit agent for XRCC1. The nick sealing of the strands is accomplished by the formation of LIG1 (DNA ligase 1) and/or LIG3/ XRCCI complex that attach to processed end of the corrected strands and reinstate the original conformation of the strand. Long patch repair comes into play when more nucleotides are involved, ranging from 2 to 12. It is hypothesized that Polymerase 𝜹 (POLD) and Polymerase 𝛆 (POLE), assisted by the PCNA (proliferating cell nuclear antigen) in conjunction with replication factor C (RFC) that acts as a stabilizer and places newly synthesized nucleotides on the DNA strand. Both the polymerases repair the DNA by employing the strand displacement synthesis mechanism. This mechanism occurs downstream a DNA strand and the 5’ is transformed into a “flap intermediate” causing it to be “displaced”. FEN1 (flap structure-specific endonuclease 1), a nuclease, removes the displaced strand and this results in a ligatable strand of DNA.Long patch repair, like short patch repair, includes the use of APE1 and PARP1 and LIG1. The repair pathway is partially determined by the amount of ATP present after the removal of the deoxyribose phosphate end. The long patch repair pathway is preferred under conditions of low ATP concentration while the short repair pathway is preferred under high concentrations of ATP. [13]

Other notable interactions include MUTYH and Replication protein A is a single strand binding protein that prevents the annealing of DNA during replication, it also plays a role as an activator for damage repair on DNA. There is a hypothetical relation between the interaction of Mismatch Repair proteins (MMR) such as MSH 2,3 and 6, MLH1, PMS1 and 2, and MUTYH in which the proposed result of their partnering is to increase susceptibility to cancer. [14]

Chemical interactions

The gene interacts with the following chemicals:

a) Carbon tetrachloride: decreased expression of MUTYH mRNA

b) Ethanol: When treated together with dronabinol) increased expression of MUTYH mRNA. When used alone, it has conflicting results of decreased and increased the MUTYH mRNA.

c) Ethinylestradiol: When used alone it results in the increased expression of MUTYH mRNA.When treated together with tetrachlorodibenzo p dioxin, there is increased expression of MUTYH mRNA.

d) Tamoxifen: affects MUTYH [15]

The table of the Gene-phenotype associations summarizes the diseases/conditions that arise from mutations in MUTYH

Phenotype/ConditionMode of Inheritance
Familial adenomatous polyposis Autosomal recessive [16]
Pilomatricoma Somatic mutation [17]
Gastric cancer Somatic mutation [18]
Endometrial cancer Biallelic germline mutation [19]

Mutations in the MUTYH gene cause an autosomal recessive disorder similar to familial adenomatous polyposis (also called MUTYH-associated polyposis). Polyps caused by mutated MUTYH do not appear until adulthood and are less numerous than those found in patients with APC gene mutations. Both copies of the MUTYH gene are mutated in individuals who have autosomal recessive familial adenomatous polyposis i.e., the mutations for the MUTYH gene is biallelic. Mutations in this gene affect the ability of cells to correct mistakes made during DNA replication. Most reported mutations in this gene cause production of a nonfunctional or low functioning glycosylase enzyme. When base excision repair in the cell is compromised, mutations in other genes build up, leading to cell overgrowth and possibly tumor formation. The two most common mutations in Caucasian Europeans are exchanges of amino acids (the building blocks of proteins) in the enzyme. One mutation replaces the amino acid tyrosine with cysteine at position 179 (also written as p.Tyr179Cys (p.Y179C)) or, when describing the nucleotide change, written as c.536A>G). The other common mutation switches the amino acid glycine with aspartic acid at position 396 (also written as p.Gly396Asp (G396D) or c.1187G>A)). [20]

The association of the gene with gastric cancer is somewhat indirect and multifactorial. When a subject is infected with Helicobacter pylori (H. pylori), the bacteria cause the formation of free oxygen radicals that are present in the gastric mucosa and this increases the propensity of the genes to incur oxidative damage . A study of 95 cases of patients who had sporadic cancers, initiated by the presence of H. pylori, and two of the 95 patients had biallelic mutation of the MUTYH gene. The somatic missense mutations for the first identified cancer occurred at codon 391, in which there was a change in the nucleotide bases from CCG (codon for amino acid proline) to TCG (codon for amino acid serine), while the second cancer had a nucleotide base change at codon 400 from CAG (codon for amino acid glutamine) to GGG (codon for amino acid arginine). The mutations were found to be highly conserved in the Nudix hydrolase domain of MUTYH. These amino acid mutations provide the basis for the somatic mutations in the gastric system. [21]

Pilomatricoma has been noted in a case that concerned two siblings who were the offspring of consanguineous parents. The siblings had a 2 base pair homozygous insertion on the MUTYH gene ( exon 13). Consequently, a frameshift occurred due to the insertion and a premature stop codon was read at 438 on the gene. Pilomatricoma was the phenotypic manifestation of this mutation. One of the siblings was also found to have rectal adenocarcinoma. It is worthy to note that CTNNB1, a gene associated with pilomatricoma, was also investigated. However, no mutations in this gene were found, thereby dismissing it as a possible cause for this case. [22]

There is an established correlation between aging and the elevation 8-oxoG concentrations, particularly in organs that exhibit reduced cell proliferation such as the kidneys, liver, brain and lungs. [23] Presence of 8-oxoG also occurs in large concentrations in patients with neurological conditions such as Alzheimer's, Parkinson's and Huntington's disease. [24] MUTYH causes immoderate formation of single stranded breaks via base excision repair, under acute oxidative stress conditions. [25] [26] When the 8-oxoguanine species accumulate and increase in concentration in the neurons, MUTYH responds by triggering their degeneration. [27]

Related Research Articles

<span class="mw-page-title-main">DNA repair</span> Cellular mechanism

DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA damage, resulting in tens of thousands of individual molecular lesions per cell per day. Many of these lesions cause structural damage to the DNA molecule and can alter or eliminate the cell's ability to transcribe the gene that the affected DNA encodes. Other lesions induce potentially harmful mutations in the cell's genome, which affect the survival of its daughter cells after it undergoes mitosis. As a consequence, the DNA repair process is constantly active as it responds to damage in the DNA structure. When normal repair processes fail, and when cellular apoptosis does not occur, irreparable DNA damage may occur, including double-strand breaks and DNA crosslinkages. This can eventually lead to malignant tumors, or cancer as per the two hit hypothesis.

<span class="mw-page-title-main">Molecular lesion</span> Damage to the structure of a biological molecule

A molecular lesion or point lesion is damage to the structure of a biological molecule such as DNA, RNA, or protein. This damage may result in the reduction or absence of normal function, and in rare cases the gain of a new function. Lesions in DNA may consist of breaks or other changes in chemical structure of the helix, ultimately preventing transcription. Meanwhile, lesions in proteins consist of both broken bonds and improper folding of the amino acid chain. While many nucleic acid lesions are general across DNA and RNA, some are specific to one, such as thymine dimers being found exclusively in DNA. Several cellular repair mechanisms exist, ranging from global to specific, in order to prevent lasting damage resulting from lesions.

<span class="mw-page-title-main">Familial adenomatous polyposis</span> Medical condition

Familial adenomatous polyposis (FAP) is an autosomal dominant inherited condition in which numerous adenomatous polyps form mainly in the epithelium of the large intestine. While these polyps start out benign, malignant transformation into colon cancer occurs when they are left untreated. Three variants are known to exist, FAP and attenuated FAP are caused by APC gene defects on chromosome 5 while autosomal recessive FAP is caused by defects in the MUTYH gene on chromosome 1. Of the three, FAP itself is the most severe and most common; although for all three, the resulting colonic polyps and cancers are initially confined to the colon wall. Detection and removal before metastasis outside the colon can greatly reduce and in many cases eliminate the spread of cancer.

DNA glycosylases are a family of enzymes involved in base excision repair, classified under EC number EC 3.2.2. Base excision repair is the mechanism by which damaged bases in DNA are removed and replaced. DNA glycosylases catalyze the first step of this process. They remove the damaged nitrogenous base while leaving the sugar-phosphate backbone intact, creating an apurinic/apyrimidinic site, commonly referred to as an AP site. This is accomplished by flipping the damaged base out of the double helix followed by cleavage of the N-glycosidic bond.

<span class="mw-page-title-main">Base excision repair</span> DNA repair process

Base excision repair (BER) is a cellular mechanism, studied in the fields of biochemistry and genetics, that repairs damaged DNA throughout the cell cycle. It is responsible primarily for removing small, non-helix-distorting base lesions from the genome. The related nucleotide excision repair pathway repairs bulky helix-distorting lesions. BER is important for removing damaged bases that could otherwise cause mutations by mispairing or lead to breaks in DNA during replication. BER is initiated by DNA glycosylases, which recognize and remove specific damaged or inappropriate bases, forming AP sites. These are then cleaved by an AP endonuclease. The resulting single-strand break can then be processed by either short-patch or long-patch BER.

<span class="mw-page-title-main">Adenomatous polyposis coli</span> Protein-coding gene in the species Homo sapiens

Adenomatous polyposis coli (APC) also known as deleted in polyposis 2.5 (DP2.5) is a protein that in humans is encoded by the APC gene. The APC protein is a negative regulator that controls beta-catenin concentrations and interacts with E-cadherin, which are involved in cell adhesion. Mutations in the APC gene may result in colorectal cancer and desmoid tumors.

<span class="mw-page-title-main">Werner syndrome helicase</span> Protein-coding gene in the species Homo sapiens

Werner syndrome ATP-dependent helicase, also known as DNA helicase, RecQ-like type 3, is an enzyme that in humans is encoded by the WRN gene. WRN is a member of the RecQ Helicase family. Helicase enzymes generally unwind and separate double-stranded DNA. These activities are necessary before DNA can be copied in preparation for cell division. Helicase enzymes are also critical for making a blueprint of a gene for protein production, a process called transcription. Further evidence suggests that Werner protein plays a critical role in repairing DNA. Overall, this protein helps maintain the structure and integrity of a person's DNA.

<span class="mw-page-title-main">XRCC1</span> Protein

DNA repair protein XRCC1, also known as X-ray repair cross-complementing protein 1, is a protein that in humans is encoded by the XRCC1 gene. XRCC1 is involved in DNA repair, where it complexes with DNA ligase III.

<span class="mw-page-title-main">Oxoguanine glycosylase</span> DNA glycosylase enzyme

8-Oxoguanine glycosylase, also known as OGG1, is a DNA glycosylase enzyme that, in humans, is encoded by the OGG1 gene. It is involved in base excision repair. It is found in bacterial, archaeal and eukaryotic species.

Missense mRNA is a messenger RNA bearing one or more mutated codons that yield polypeptides with an amino acid sequence different from the wild-type or naturally occurring polypeptide. Missense mRNA molecules are created when template DNA strands or the mRNA strands themselves undergo a missense mutation in which a protein coding sequence is mutated and an altered amino acid sequence is coded for.

<span class="mw-page-title-main">ERCC6</span> Gene of the species Homo sapiens

DNA excision repair protein ERCC-6 is a protein that in humans is encoded by the ERCC6 gene. The ERCC6 gene is located on the long arm of chromosome 10 at position 11.23.

<span class="mw-page-title-main">DNA-3-methyladenine glycosylase</span> Protein-coding gene in the species Homo sapiens

DNA-3-methyladenine glycosylase also known as 3-alkyladenine DNA glycosylase (AAG) or N-methylpurine DNA glycosylase (MPG) is an enzyme that in humans is encoded by the MPG gene.

<span class="mw-page-title-main">NTHL1</span> Protein-coding gene in the species Homo sapiens

Endonuclease III-like protein 1 is an enzyme that in humans is encoded by the NTHL1 gene.

<span class="mw-page-title-main">NEIL1</span> Protein-coding gene in the species Homo sapiens

Endonuclease VIII-like 1 is an enzyme that in humans is encoded by the NEIL1 gene.

<span class="mw-page-title-main">MBD4</span> Protein-coding gene in the species Homo sapiens

Methyl-CpG-binding domain protein 4 is a protein that in humans is encoded by the MBD4 gene.

<span class="mw-page-title-main">SMUG1</span> Protein-coding gene in the species Homo sapiens

Single-strand selective monofunctional uracil DNA glycosylase is an enzyme that in humans is encoded by the SMUG1 gene. SMUG1 is a glycosylase that removes uracil from single- and double-stranded DNA in nuclear chromatin, thus contributing to base excision repair.

<span class="mw-page-title-main">8-Oxo-2'-deoxyguanosine</span> Chemical compound

8-Oxo-2'-deoxyguanosine (8-oxo-dG) is an oxidized derivative of deoxyguanosine. 8-Oxo-dG is one of the major products of DNA oxidation. Concentrations of 8-oxo-dG within a cell are a measurement of oxidative stress.

DNA damage is an alteration in the chemical structure of DNA, such as a break in a strand of DNA, a nucleobase missing from the backbone of DNA, or a chemically changed base such as 8-OHdG. DNA damage can occur naturally or via environmental factors, but is distinctly different from mutation, although both are types of error in DNA. DNA damage is an abnormal chemical structure in DNA, while a mutation is a change in the sequence of base pairs. DNA damages cause changes in the structure of the genetic material and prevents the replication mechanism from functioning and performing properly. The DNA damage response (DDR) is a complex signal transduction pathway which recognizes when DNA is damaged and initiates the cellular response to the damage.

<span class="mw-page-title-main">Hereditary cancer syndrome</span> Inherited genetic condition that predisposes a person to cancer

A hereditary cancer syndrome is a genetic disorder in which inherited genetic mutations in one or more genes predispose the affected individuals to the development of cancer and may also cause early onset of these cancers. Hereditary cancer syndromes often show not only a high lifetime risk of developing cancer, but also the development of multiple independent primary tumors.

MUTYH-associated polyposis is an autosomal recessive polyposis syndrome. The disorder is caused by mutations in both alleles of the DNA repair gene, MUTYH. The MUTYH gene encodes a base excision repair protein, which corrects oxidative damage to DNA. Affected individuals have an increased risk of colorectal cancer, precancerous colon polyps (adenomas) and an increased risk of several additional cancers. About 1–2 percent of the population possess a mutated copy of the MUTYH gene, and less than 1 percent of people have the MUTYH associated polyposis syndrome. The presence of 10 or more colon adenomas should prompt consideration of MUTYH-associated polyposis, familial adenomatous polyposis and similar syndromes.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000132781 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000028687 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ "Entrez Gene: MUTYH mutY homolog (E. coli)".
  6. 1 2 GeneCard for MUTYH
  7. ↑ Slupska MM, Baikalov C, Luther WM, Chiang JH, Wei YF, Miller JH (July 1996). "Cloning and sequencing a human homolog (hMYH) of the Escherichia coli mutY gene whose function is required for the repair of oxidative DNA damage". Journal of Bacteriology. 178 (13): 3885–92. doi:10.1128/jb.178.13.3885-3892.1996. PMC   232650 . PMID   8682794.
  8. ↑ Online Mendelian Inheritance in Man (OMIM): MUTYH - 604933
  9. ↑ Shinmura K, Yokota J (August 2001). "The OGG1 gene encodes a repair enzyme for oxidatively damaged DNA and is involved in human carcinogenesis". Antioxidants & Redox Signaling. 3 (4): 597–609. doi:10.1089/15230860152542952. PMID   11554447.
  10. ↑ Kitsera N, Stathis D, Lühnsdorf B, Müller H, Carell T, Epe B, Khobta A (August 2011). "8-Oxo-7,8-dihydroguanine in DNA does not constitute a barrier to transcription, but is converted into transcription-blocking damage by OGG1". Nucleic Acids Research. 39 (14): 5926–34. doi:10.1093/nar/gkr163. PMC   3152326 . PMID   21441539.
  11. ↑ Oka S, Leon J, Tsuchimoto D, Sakumi K, Nakabeppu Y (February 2015). "MUTYH, an adenine DNA glycosylase, mediates p53 tumor suppression via PARP-dependent cell death". Oncogenesis. 4 (2): e142. doi:10.1038/oncsis.2015.4. PMC   4338427 . PMID   25706342.
  12. 1 2 3 Parker A, Gu Y, Mahoney W, Lee SH, Singh KK, Lu AL (February 2001). "Human homolog of the MutY repair protein (hMYH) physically interacts with proteins involved in long patch DNA base excision repair". The Journal of Biological Chemistry. 276 (8): 5547–55. doi: 10.1074/jbc.M008463200 . PMID   11092888.
  13. ↑ Kim YJ, Wilson DM (January 2012). "Overview of base excision repair biochemistry". Current Molecular Pharmacology. 5 (1): 3–13. doi:10.2174/1874467211205010003. PMC   3459583 . PMID   22122461.
  14. ↑ Niessen RC, Sijmons RH, Ou J, Olthof SG, Osinga J, Ligtenberg MJ, Hogervorst FB, Weiss MM, Tops CM, Hes FJ, de Bock GH, Buys CH, Kleibeuker JH, Hofstra RM (March 2006). "MUTYH and the mismatch repair system: partners in crime?" (PDF). Human Genetics. 119 (1–2): 206–11. doi:10.1007/s00439-005-0118-5. PMID   16408224. S2CID   22651739.
  15. ↑ "MUTYH". Entrez Gene.[ permanent dead link ]
  16. ↑ Online Mendelian Inheritance in Man (OMIM): Familial adenomatous polyposis 2; FAP2 - 608456
  17. ↑ Online Mendelian Inheritance in Man (OMIM): Pilomatricoma - 132600
  18. ↑ Online Mendelian Inheritance in Man (OMIM): Gastric Cancer - 613659
  19. ↑ Tricarico R, Bet P, Ciambotti B, Di Gregorio C, Gatteschi B, Gismondi V, Toschi B, Tonelli F, Varesco L, Genuardi M (February 2009). "Endometrial cancer and somatic G>T KRAS transversion in patients with constitutional MUTYH biallelic mutations". Cancer Letters. 274 (2): 266–70. doi:10.1016/j.canlet.2008.09.022. PMID   18980800.
  20. ↑ Aretz S, Tricarico R, Papi L, Spier I, Pin E, Horpaopan S, Cordisco EL, Pedroni M, Stienen D, Gentile A, Panza A, Piepoli A, de Leon MP, Friedl W, Viel A, Genuardi M (July 2014). "MUTYH-associated polyposis (MAP): evidence for the origin of the common European mutations p.Tyr179Cys and p.Gly396Asp by founder events". European Journal of Human Genetics. 22 (7): 923–9. doi:10.1038/ejhg.2012.309. PMC   4060104 . PMID   23361220.
  21. ↑ Kim CJ, Cho YG, Park CH, Kim SY, Nam SW, Lee SH, Yoo NJ, Lee JY, Park WS (September 2004). "Genetic alterations of the MYH gene in gastric cancer". Oncogene. 23 (40): 6820–2. doi: 10.1038/sj.onc.1207574 . PMID   15273732.
  22. ↑ Baglioni S, Melean G, Gensini F, Santucci M, Scatizzi M, Papi L, Genuardi M (April 2005). "A kindred with MYH-associated polyposis and pilomatricomas". American Journal of Medical Genetics. Part A. 134A (2): 212–4. doi:10.1002/ajmg.a.30585. PMID   15690400. S2CID   21866377.
  23. ↑ Møller P, Løhr M, Folkmann JK, Mikkelsen L, Loft S (May 2010). "Aging and oxidatively damaged nuclear DNA in animal organs". Free Radical Biology & Medicine. 48 (10): 1275–85. doi:10.1016/j.freeradbiomed.2010.02.003. PMID   20149865.
  24. ↑ Bjørge MD, Hildrestrand GA, Scheffler K, Suganthan R, Rolseth V, Kuśnierczyk A, Rowe AD, Vågbø CB, Vetlesen S, Eide L, Slupphaug G, Nakabeppu Y, Bredy TW, Klungland A, Bjørås M (December 2015). "Synergistic Actions of Ogg1 and Mutyh DNA Glycosylases Modulate Anxiety-like Behavior in Mice" (PDF). Cell Reports. 13 (12): 2671–8. doi: 10.1016/j.celrep.2015.12.001 . PMID   26711335.
  25. ↑ Oka S, Ohno M, Tsuchimoto D, Sakumi K, Furuichi M, Nakabeppu Y (2008). "Two distinct pathways of cell death triggered by oxidative damage to nuclear and mitochondrial DNAs". The EMBO Journal. 27 (2): 421–32. doi:10.1038/sj.emboj.7601975. PMC   2234344 . PMID   18188152.
  26. ↑ Oka S, Nakabeppu Y (2011). "DNA glycosylase encoded by MUTYH functions as a molecular switch for programmed cell death under oxidative stress to suppress tumorigenesis". Cancer Science. 102 (4): 677–82. doi: 10.1111/j.1349-7006.2011.01869.x . PMID   21235684.
  27. ↑ Sheng Z, Oka S, Tsuchimoto D, Abolhassani N, Nomaru H, Sakumi K, Yamada H, Nakabeppu Y (2012). "8-Oxoguanine causes neurodegeneration during MUTYH-mediated DNA base excision repair". The Journal of Clinical Investigation. 122 (12): 4344–61. doi:10.1172/JCI65053. PMC   3533558 . PMID   23143307.

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