bio exam 2

origin of replication

binding sites of proteins to initiate replication process

direct damage reversal

• repair of O6-methylguanine by O6-methylguanine DNA
  methyltransferase (MGMT)

• photoreactivation of UV-induced pyrimidine dimers by photolyase (proks)

mismatch repair (MMR)

• mismatches due to DNA replication errors, such as incorporating a non-complementary base

• after S, G2 into S

• key players: MutS, MutL, & MutH (bacteria) + MSH & MLH (humans) → proteins

base excision repair (BER)

• small, non-helix-distorting base lesions caused by deamination, oxidation, or alkylation damage

• key players: DNA glycosylases (initiates), AP endonuclease, DNA pol, ligase

nucleotide excision repair (NER)

• bulky, helix-distorting lesions, such as those caused by UV light-induced pyrimidine dimers or interaction of DNA with carginogens

• key players: XPC/XPA-XPG, TFIIH complex

translesion synthesis (TLS)

• bulky DNA lesions that stall replication forks

• during S

• key players: pol V (bacteria), many pol in euks

non-homologous end joining (NHEJ)

• for double-strand breaks (DSBs)

• more error-prone than homologous directed repair

• directly ligates broken ends without homologous template

• esp during G1

• key players: Ku70/80 heterodimer, DNA-PKcs

homologous directed repair (HDR)

• for double-strand breaks (DSBs)

• esp S + G2

• uses a sister chromatid as a template

• key players: BRCA 1/2, RAD51

site-specific recombinations

• B cell development

• generates antibody diversity by rearranging gene segments

• light chain: V+J

• heavy chains: D+J, then V+DJ

combination of different light/heavy chains

generate different immunoglobulins

class switch recombination

• switch region of antibodies

• replace heavy-chain constant region gene for another downstream of it

• initiated by activation-induced deaminase → double-stranded DNA breaks that are rejoined

• antibodies adapt to pathogens

somatic hypermutation

produces multiple point mutations within rearranged variable regionsof both heavy and light chains

activation-induced deaminase (AID)

• in somatic hypermutation + class switch recombination

• base-excision repair of C to U in DNA

IgM

activates complement, a first line of defense against invading cells or viruses

IgG

activates complement and binds to phagocytic cells + can cross the placenta

IgA

secreted into nasal mucus + saliva to eliminate bacteria and viruses + breast milk

IgE

protect against parasitic infections + in allergies

Ku70-Ku80 heterodimer

high affinity for ends of DNA with blunt or sticky overhangs + recruits several proteins (ligase) (NHEJ)

BRCA1

facilitates DSB ends to ssDNA overhangs (HDR)

BRCA2

encodes a protein that recruits RAD51 to ssDNA overhangs (HDR)

RAD51

repairing DNA double-strand breaks + maintaining genetic stability