DNA-(apurinic or apyrimidinic site) lyase is an
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
that in humans is encoded by the ''APEX1''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
Apurinic/apyrimidinic (AP) sites (also called "abasic sites") occur frequently in DNA molecules by spontaneous hydrolysis, by DNA damaging agents or by DNA glycosylases that remove specific abnormal bases. AP sites are pre-mutagenic lesions that can prevent normal DNA replication. All cells, from simple prokaryotes to humans, have evolved systems to identify and repair such sites. Class II AP endonucleases cleave the phosphodiester backbone 5' to the AP site, thereby initiating a process known as
base excision repair
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 t ...
(BER). The APEX gene (alternatively named APE1, HAP1, APEN) encodes the major AP endonuclease in human cells. Splice variants have been found for this gene; all encode the same protein.
Interactions
APEX1 has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
with
MUTYH
''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 backbon ...
,
Flap structure-specific endonuclease 1
Flap endonuclease 1 is an enzyme that in humans is encoded by the ''FEN1'' gene.
Function
The protein encoded by this gene removes 5' overhanging "flaps" (or short sections of single stranded DNA that "hang off" because their nucleotide bases a ...
and
XRCC1
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.
Function
XRCC1 is invol ...
.
Aging
Deficiency of APEX1 causes accummulation of
DNA damage
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 da ...
leading to both
cellular senescence
Cellular senescence is a phenomenon characterized by the cessation of cell division. In their experiments during the early 1960s, Leonard Hayflick and Paul Moorhead found that normal human fetal fibroblasts in culture reach a maximum of approxi ...
and features of premature
aging
Ageing ( BE) or aging ( AE) is the process of becoming older. The term refers mainly to humans, many other animals, and fungi, whereas for example, bacteria, perennial plants and some simple animals are potentially biologically immortal. In ...
.
This finding is consistent with the theory that DNA damage is a primary cause of aging.
References
Further reading
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External links
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