DNA Repair Mechanisms Tournament
Two onboarding diagrams orient you in DNA repair. Then eight MCAT-DoK quiz rounds: MMR + Lynch syndrome (MLH1/MSH2), NER + xeroderma pigmentosum, BER mechanism, HR vs NHEJ for double-strand breaks, BRCA1/2 + PARP inhibitor synthetic lethality, ATM kinase + ataxia telangiectasia, and MGMT in temozolomide response.
Where the Mismatch repair fits in DNA Repair
Reactome's DNA Repair overview shows the seven major sub-pathways the genome uses to handle different damage types. Mismatch repair (MMR) is the Lynch syndrome / hypermutated tumor pathway and one of the most testable on the MCAT. Click the highlighted MMR box to enter the tournament.
Click the highlighted Mismatch repair box to continue.
What this tournament tests
Each task maps to a distinct MCAT cognitive demand. The first two orient you in the broader topology; the next eight test the high-yield mechanism, regulation, sequence and quantitative reasoning that consistently appear on test day.
The Bigger Picture
Anchor MMR within Reactome's DNA Repair map alongside BER, NER, HR, and NHEJ.
Whole-Pathway Overview
Pan and zoom the curated WikiPathways mismatch repair figure before answering questions.
Fill in the Blank
Recall MLH1 + MSH2 as the most common Lynch syndrome genes.
Xeroderma Pigmentosum Disruptor
Predict why NER loss causes severe UV photosensitivity and early skin cancer.
Sequence Ordering
Order BER from glycosylase recognition to ligation of the repaired strand.
Match the Pairs
Pair each repair pathway with its substrate, key components, and clinical syndrome.
Numeric Input
Estimate the daily DNA damage flux per cell.
Select All That Apply
Identify true statements about BRCA1/2, PARP inhibitors, p53, and ATM kinase.
Odd One Out
Distinguish double-strand break repair components (BRCA1/2/RAD51) from MMR (MLH1).
PARP / BRCA Synthetic Lethality Disruptor
Predict why olaparib selectively kills BRCA-deficient tumor cells.
Public leaderboard
Your score posts to a global, persistent leaderboard scored by points first, time as tiebreaker.
DNA repair in 60 seconds
Five major repair systems handle different damage classes. BER fixes single damaged bases (oxidation, deamination, alkylation). NER excises a ~30-nt patch around bulky helix-distorting lesions like UV pyrimidine dimers. MMR corrects replication mismatches and slippage at microsatellites.
Double-strand break repair has two arms: homologous recombination (HR) uses a sister chromatid template (S/G2 phase) and is precise; BRCA1/2 + RAD51 are central. NHEJ works in any cell-cycle phase but is error-prone; Ku + DNA-PKcs + LIG4 are central.
Direct reversal: MGMT removes O6-methylguanine. Tumors that silence MGMT (by promoter methylation) cannot remove the alkylation lesions of temozolomide - explaining why MGMT methylation status predicts response in glioblastoma.
Inherited repair syndromes are a textbook MCAT category: Lynch (MMR) -> colorectal + endometrial cancer; XP (NER) -> UV photosensitivity + skin cancer; BRCA1/2 (HR) -> breast + ovarian cancer (PARP inhibitor synthetic lethality); ataxia telangiectasia (ATM) -> cerebellar ataxia + lymphoma + radiation sensitivity.
FAQ
What is microsatellite instability (MSI)?
MMR-deficient tumors accumulate length variation at microsatellite repeats (e.g. mononucleotide tracts in BAT25, BAT26). This 'MSI-H' phenotype is a marker of MMR loss - hereditary (Lynch) or sporadic (MLH1 promoter methylation in colorectal cancer). MSI-H tumors are HYPERMUTATED, generating many neoantigens, which is why they respond well to immune checkpoint inhibitors (pembrolizumab).
What is synthetic lethality?
Two genes are individually tolerable when knocked out, but lethal when both are lost simultaneously. PARP inhibitors + BRCA mutations is the prototype: PARP normally repairs single-strand breaks; PARP inhibition causes replication forks to collapse into double-strand breaks; BRCA-deficient cells can't repair these via HR -> tumor cell death. Normal cells (BRCA wild-type) tolerate PARP inhibition because HR remains intact.
Why is NHEJ called 'error-prone'?
NHEJ ligates the broken ends together with minimal processing - sometimes losing or gaining nucleotides at the junction. This is what makes V(D)J recombination work in lymphocytes (controlled NHEJ generates antibody and TCR diversity), but in any other context it produces small insertions / deletions. HR uses a homologous template and is essentially error-free, but it requires a sister chromatid (S/G2 only).
Do I need an account to play?
No. The tournament is fully public. You get a randomized handle and your score posts to the public leaderboard at the bottom of this page.
Keep going
DNA damage checkpoints (ATM, ATR, CHK1/2, p53) integrate repair with the cell cycle.
When damage cannot be repaired, p53 routes cells through the intrinsic apoptotic pathway.
Overview diagram: Reactome Pathway R-HSA-73894, licensed CC BY 4.0.