Answer to DNA Repair Exam Question 4, November, 1998

I counted both the yeast and mammalian names in the following table as correct:

Proteins demonstrated to be important for NHEJ
Yeast gene name Mammalian gene name Protein & function
? XRCC4 Unknown function
HDF2 XRCC5 Ku80 (part of DNA protein kinase)
HDF1 XRCC6 Ku70 (part of DNA protein kinase)
? XRCC7 Catalytic subunit of DNA protein kinase
RAD50 RAD50 Stimulates Mre11 exonuclease
MRE11 MRE11 3' to 5' exonuclease
XRS2 NBS1 Interacts with Rad50, Mre11

In addition, I gave extra credit (but not beyond the maximum score of 8 points for this question) if you mentioned DNaseIV/FEN-1 and/or DNA ligase, both of which may be involved in the final stages of NHEJ, although there is not yet any genetic evidence for their involvement.

Note that, at this point, the roles of KU and of the DNA protein kinase in NHEJ are not clear. From genetic evidence we know they are required, but we don't know exactly what they do. A possible role for the Mre11 exonuclease seems more clear from the recent studies in the Gellert laboratory, but that role is still not proved.

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