Editing Programmed cell death (section)

==DNA damage and apoptosis==

[[File:DNA damage can lead to apoptosis or cancer.jpg|thumb|500px|Oxidative stress or environmental insults can lead to DNA damage in replicating cells and this can result in apoptosis or cancer.]]

[[DNA repair|Repair of DNA damages]] and [[apoptosis]] are two enzymatic processes essential for maintaining [[genome]] integrity in humans.  Cells that are deficient in DNA repair tend to accumulate [[DNA damage (naturally occurring)|DNA damages]], and when such cells are also defective in apoptosis they tend to survive even with excess DNA damage.<ref name="Bernstein2002">{{Cite journal |pmid=12052432 |date=2002 |last1=Bernstein |first1=C. |last2=Bernstein |first2=H. |last3=Payne |first3=C. M. |last4=Garewal |first4=H. |title=DNA repair/Pro-apoptotic dual-role proteins in five major DNA repair pathways: Fail-safe protection against carcinogenesis |journal=Mutation Research |volume=511 |issue=2 |pages=145–178 |doi=10.1016/s1383-5742(02)00009-1 }}</ref>  Replication of DNA in such cells leads to [[mutation]]s and these mutations may cause cancer (see Figure).  Several enzymatic pathways have evolved for repairing different kinds of DNA damage, and it has been found that in five well studied DNA repair pathways particular enzymes have a dual role, where one role is to participate in repair of a specific class of damages and the second role is to induce apoptosis if the level of such DNA damage is beyond the cell's repair capability.<ref name = Bernstein2002/>  These dual role proteins tend to protect against development of cancer.  Proteins that function in such a dual role for each repair process are: (1) [[DNA mismatch repair]], [[MSH2]], [[MSH6]], [[MLH1]] and [[PMS2]]; (2) [[base excision repair]], [[APEX1]] (REF1/APE), [[PARP1|poly(ADP-ribose) polymerase]] (PARP); (3) [[nucleotide excision repair]], [[XPB]], XPD ([[ERCC2]]), [[p53]], p33([[ING1]]b); (4) [[non-homologous end joining]], the catalytic subunit of [[DNA-PKcs|DNA-PK]]; (5) [[homologous recombination]]al repair, [[BRCA1]], [[ATM serine/threonine kinase|ATM]], [[ataxia telangiectasia and Rad3 related|ATR]], [[Werner syndrome helicase|WRN]], [[Bloom syndrome protein|BLM]], [[KAT5|Tip60]], [[p53]].