Human MMR

Question 1

How are mismatches detected?

Answer 1

by heterodimers mutSHa and SHb; mutSa has affinity for small loops (2nt) and SHB large loops (13 nt)

Question 2

MLH is recruited to the MutSH heterodimer complex; it likely has weak endonuc activity; disturbs PCNA and stops replication; recruits exonucs

Answer 2

ya

Question 3

there is no MutH in human MMR

Answer 3

ya

Question 4

heterdimers of MutSH follow polymerase to check for problems; if it finds one a heterdimer of mutL is bound and finds/releases PCNA clamp–>no PCNA, pol delta/epsilon loses processivity and is released; MH and MLH recruit helicases and exonucs to degrade newly synthed DNA

Answer 4

ya

Question 5

errors in human mmr–caused by what?

Answer 5

mutations in MSH2 and MLH1–causes colon cancer

Question 6

why is nonreplicative mutations (UV damage, alkylating agents, etc) a problem?

Answer 6

happens before DNA replication–no way to tell which strand is new vs old